US2005143594A1PendingUtilityA1
Process for preparing resorcinol derivatives
Priority: Mar 15, 2000Filed: Jan 14, 2005Published: Jun 30, 2005
Est. expiryMar 15, 2020(expired)· nominal 20-yr term from priority
Y02P20/55C07C 2601/14C07C 2601/18C07D 317/72C07C 37/07C07C 45/59Y10S977/926C07C 49/747C07C 45/71C07C 37/06
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Claims
Abstract
The present invention relates to an improved process for preparing 4-substituted resorcinol derivatives, and intermediate compounds useful in the preparation of such resorcinol derivatives.
Claims
exact text as granted — not AI-modified1 . A process for preparing a compound of formula (6)
wherein W is hydrogen or a protecting group;
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 6 )cycloalkyl ring or (C,-C,)cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -CC 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal;
comprising reacting a compound of formula (5) or (5′)
wherein Q is halo, and W, X and Y are as defined above, with a base to form the compound of formula (6).
2 . The process according to claim 1 , wherein Q is bromo, iodo or chloro.
3 . The process according to claim 1 , wherein Q is bromo.
4 . A process for preparing a compound of formula (7)
wherein W is hydrogen or a protecting group;
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal;
comprising reacting a compound of formula (5) or (5′)
wherein Q is halo, and W, X and Y are as defined above, with a base to form the compound of formula (7).
5 . The process according to claim 4 , wherein Q is bromo, iodo or chloro.
6 . The process according to claim 4 , wherein Q is bromo.
7 . The process according to claim 1 or claim 4 , wherein the compound of formula (5) is prepared by reacting the compound of formula (4)
wherein W, X and Y are as defined above, with a halogenating agent to form the compound of formula (5).
8 . The process according to claim 7 , wherein the halogenating agent is a brominating agent.
9 . The process according to claim 8 , wherein the brominating agent is N-bromosuccinimide.
10 . The process according to claim 7 , wherein the compound of formula (4) is prepared by reacting a compound of formula (2)
with a compound of formula (3)
wherein W, X and Y are as defined above, in the presence of a base to form the compound of formula (4).
11 . A process for preparing a compound of formula (5)
wherein Q is halo;
wherein W is a protecting group;
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal;
comprising reacting the compound of formula (4)
wherein W, X and Y are as defined above, with a halogenating agent to form the compound of formula (5).
12 . The process according to claim 11 , wherein the halogenating agent is a brominating agent.
13 . The process according to claim 12 , wherein the brominating agent is N-bromosuccinimide.
14 . The process according to claim 11 , wherein the compound of formula (4) is prepared by reacting a compound of formula (2)
with a compound of formula (3)
wherein W, X and Y are as defined above, in the presence of a base to form the compound of formula (4).
15 . A process for preparing a compound of formula (5′)
wherein Q is halo;
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 5 )(N(R 4 ) 2 )(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal;
comprising reacting the compound of formula (4)
wherein W is H, and X and Y are as defined above, with a halogenating agent to form the compound of formula (5′).
16 . The process according to claim 15 , wherein the halogenating agent is a brominating agent.
17 . The process according to claim 16 , wherein the brominating agent is N-bromosuccinimide.
18 . The process according to claim 15 , wherein the compound of formula (4) is prepared by reacting a compound of formula (2)
with a compound of formula (3)
wherein W, X and Y are as defined above, in the presence of a base to form the compound of formula (4).
19 . A process for preparing a compound of formula (4)
wherein W is hydrogen or a protecting group;
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 ) alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 ) alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal;
comprising reacting a compound of formula (2)
with a compound of formula (3)
wherein X and Y are as defined above, in the presence of a base to form the compound of formula (4).
20 . A process for preparing a compound of formula I(a)
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (Cl-C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O(C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal; comprising:
(a) reacting a compound of formula (5) or (5′)
wherein Q is halo, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (6); and
(b) where W is H, reducing the compound of formula (6) so formed to form the compound of formula I(a); or
(c) where W is a protecting group, reducing the compound of formula (6) so formed and removing the protecting group to form the compound of formula I(a).
21 . A process for preparing a compound of formula I(a)
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(N R 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; or a ketal; comprising:
(a) reacting a compound of formula (5) or (5′)
wherein Q is halo, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (7); and
(b) where W is H, hydrogenating the compound of formula (7) so formed to form the compound of formula I(a); or
(c) where W is a protecting group, hydrogenating the compound of formula (7) so formed and removing the protecting group to form the compound of formula I(a).
22 . A process for preparing a compound of formula 1(a)
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 5 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ); R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal; comprising:
(a) reacting a compound of formula (5) or (5′)
wherein Q is halo, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (6);
(b) reacting the compound of formula (6) so formed with a base to form a compound of formula (7); and
(c) where W is H, hydrogenating the compound of formula (7) so formed to form the compound of formula I(a); or
(d) where W is a protecting group, hydrogenating the compound of formula (7) so formed and removing the protecting group to form the compound of formula I(a).
23 . A process for preparing a compound of formula I(a)
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 ) alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal; comprising:
(a) reacting a compound of formula (5) or (5′)
wherein Q is halo, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (6);
(b) reacting the compound of formula (6) so formed with a base to form a compound of formula (7); and
(c) where W is H, hydrogenating the compound of formula (7) so formed to form the compound of formula I(a); or
(d) where W is a protecting group, removing the protecting group from compound (7) so formed to form the compound of formula 1(b)
and hydrogenating the compound of formula I(b) so formed to form the compound of formula I(a).
24 . A process for preparing a compound of formula I(a)
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO-NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON—(C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O-(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal; comprising:
(a) reacting a compound of formula (5) or (5′)
wherein Q is halo, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (7); and
(b) where W is H, hydrogenating the compound of formula (7) so formed to form the compound of formula I(a); or
(c) where W is a protecting group, removing the protecting group from compound (7) so formed to form the compound of formula I(b)
and hydrogenating the compound of formula I(b) so formed to form the compound of formula I(a).
25 . A process for preparing a compound of formula I(b)
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal; comprising:
(a) reacting a compound of formula (5) or (5′)
wherein Q is halo, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula (6);
(b) reacting the compound of formula (6) so formed with a base to form a compound of formula I(b) when W is H, and a compound of formula (7) when W is a protecting group; and
(c) when W is a protecting group, removing the protecting group from the compound of formula (7) so formed to form the compound of formula I(b).
26 . A process for preparing a compound of formula I(b)
wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 5 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C,-C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O-(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal; comprising:
(a) reacting a compound of formula (5) or (5′)
wherein Q is halo, W is hydrogen or a protecting group, and X and Y are as defined above, with a base to form a compound of formula 1(b) when W is H, and a compound of formula (7) when W is a protecting group; and
(b) when W is a protecting group, removing the protecting group from the compound of formula (7) so formed to form the compound of formula I(b).
27 . The process of claim 1 , wherein X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring which is optionally substituted.
28 . The process of claim 27 , wherein the (C 4 -C 8 )cycloalkyl or (C 5 -C 8 )cycloalkenyl ring is substituted by one to three independently selected groups Z.
29 . The process of claim 27 , wherein X and Y are taken together with the carbon to which they are attached to form a cyclohexyl or cyclohexenyl ring.
30 . The process of claim 27 , wherein X and Y are taken together with the carbon to which they are attached to form a cyclopentyl or cyclopentenyl ring.
31 . The process of claim 27 , wherein the (C 4 -C 8 )cycloalkyl or (C 5 -C 8 )cycloalkenyl ring is not substituted.
32 . The process of claim 27 , wherein the (C 4 -C 8 )cycloalkyl or (C 5 -C 8 )cycloalkenyl ring is monosubstituted.
33 . The process of claim 27 , wherein the (C 4 -C 8 )cycloalkyl or (C 5 -C 8 )cycloalkenyl ring is disubstituted.
34 . The process of claim 29 , wherein the cyclohexyl or cyclohexenyl ring is monosubstituted at the 3- or 4-position.
35 . The process of claim 30 , wherein the cyclopentyl or cyclopentenyl ring is monosubstituted at the 3-position.
36 . A compound having the structure of formula (4),
wherein W is hydrogen or a protecting group; and wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal.
37 . The compound of claim 36 , having the structure of formula (4a),
wherein W is as defined above, and n is 0,1, 2 or 3.
38 . The compound of claim 37 , having the structure of formula (4b) or (4c).
wherein W is as defined above.
39 . The compound of claim 36 , having the structure of formula (4d)
wherein W and Z are as defined above, and wherein n is 0, 1, 2 or 3.
40 . The compound of claim 39 , having the structure of formula (4e) or (4f).
wherein W and Z are as defined above.
41 . The compound of claim 36 , having the structure of formula (4g),
wherein W and Z are as defined above and wherein n is 0, 1, 2 or 3.
42 . The compound of claim 41 , having the structure of formula (4h) or (4i).
wherein W and Z are as defined above.
43 . A compound having the structure of formula (5),
wherein Q is halo; wherein W is hydrogen or a protecting group; and wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 8 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ); R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O)(C 1 -C 6 )alkyl-; R 4 S(O)R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal.
44 . The compound of claim 43 , having the structure of formula (5a)
wherein Q and W are as defined above, and n is 0, 1, 2, or 3.
45 . The compound of claim 44 , having the structure of formula (5b) or (5c)
wherein Q and W are as defined above.
46 . The compound of claim 43 , having the structure of formula (5d)
wherein a, W and Z are as defined above, and n is 0, 1, 2, or 3.
47 . The compound of claim 46 , having the structure of formula (5e) or (5f),
where Q, W and Z are as defined above.
48 . The compound of claim 43 , having the structure of formula (5g),
wherein Q, W and Z are as defined above, and n is 0, 1, 2, or 3.
49 . The compound of claim 48 , having the structure of formula (5h) or (5i),
wherein Q, W and each Z are as defined above.
50 . The compound of claim 43 , wherein Q is bromo, iodo or chloro.
51 . The compound of claim 43 , wherein Q is bromo.
52 . A compound having the structure of formula (5′)
wherein Q is halo; and wherein X and Y are each independently selected from hydrogen, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, or X and Y are taken together with the carbon to which they are attached to form a (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring, provided that the (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is not aromatic;
and wherein the (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, (C 4 -C 8 )cycloalkyl ring or (C 5 -C 8 )cycloalkenyl ring is optionally substituted by one to three independently selected groups Z, where Z is selected from the group consisting of cyano; halo; (C 1 -C 6 )alkyl; aryl; (C 2 -C 9 )heterocycloalkyl; (C 2 -C 9 )heteroaryl; aryl(C 1 -C 6 )alkyl-; ═O; ═CHO(C 1 -C 6 )alkyl; amino; hydroxy; (C 1 -C 6 )alkoxy; aryl(C 1 -C 6 )alkoxy-; (C 1 -C 6 )acyl; (C 1 -C 6 )alkylamino-; aryl(C 1 -C 6 )alkylamino-; amino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy-CO—NH—; (C 1 -C 6 )alkylamino-CO—; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; hydroxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl-; (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl-; nitro; cyano(C 1 -C 6 )alkyl-; halo(C 1 -C 6 )alkyl-; nitro(C 1 -C 6 )alkyl-; trifluoromethyl; trifluoromethyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )acylamino-; (C 1 -C 6 )acylamino(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamino-; amino(C 1 -C 6 )acyl-; amino(C 1 -C 6 )acyl(C 1 -C 6 )alkyl-; (C 1 -C 6 )alkylamino(C 1 -C 6 )acyl-; ((C 1 -C 6 )alkyl) 2 amino(C 1 -C 6 )acyl-; —CO 2 R 2 ; —(C 1 -C 6 )alkyl-CO 2 R 2 ; —C(O)N(R 2 ) 2 ; —(C 1 -C 6 )alkyl-C(O)N(R 2 ) 2 ; R 2 ON═; R 2 ON═(C 1 -C 6 )alkyl-; R 2 ON═CR 2 (C 1 -C 6 )alkyl-; —NR 2 (OR 2 ); —(C 1 -C 6 )alkyl-NR 2 (OR 2 ); —C(O)(NR 2 OR 2 ); —(C 1 -C 6 )alkyl-C(O)(NR 2 OR 2 ); —S(O) m R 2 ; wherein each R 2 is independently selected from hydrogen, (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—, wherein R 3 is (C 1 -C 6 )alkyl, aryl, or aryl(C 1 -C 6 )alkyl-; R 3 C(O)O—(C 1 -C 6 )alkyl-; R 4 R 5 N—C(O)—O—; R 4 R 5 NS(O) 2 —; R 4 R 5 NS(O) 2 (C 1 -C 6 )alkyl-; R 4 S(O) 2 R 5 N—; R 4 S(O) 2 R 5 N(C 1 -C 6 )alkyl-; wherein m is 0, 1 or 2, and R 4 and R 5 are each independently selected from hydrogen or (C 1 -C 6 )alkyl; —C(═NR 6 )(N(R 4 ) 2 ); —(C 1 -C 6 )alkyl-C(═NR 6 )(N(R 4 ) 2 ) wherein R 6 represents OR 2 or R 2 wherein R 2 is defined as above; —OC(O)aryl(C 1 -C 6 )alkyl; —NH(C 1 -C 6 )alkyl; aryl(C 1 -C 6 )alkyl-HN—; and a ketal.Join the waitlist — get patent alerts
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