US2003069422A1PendingUtilityA1
Process for preparation of pyrazolo[4,3-d]pyrimidin-7-ones and intermediates thereof
Priority: Oct 12, 1998Filed: Sep 23, 2002Published: Apr 10, 2003
Est. expiryOct 12, 2018(expired)· nominal 20-yr term from priority
A61P 15/10A61P 15/00C07D 487/04C07D 295/26C07D 487/00
49
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Claims
Abstract
A process is provided for the preparation of a compound of formulae (IA) (sidenafil) and (IB) comprising reacting a compound of formula (IIA) and (IIB) respectively in the presence of —OR, wherein R in the case of formation of compound (IA) is CH 2 CH 3 and R in the case of formation of compound (IB) is CH 2 CH 2 CH 3 , where X is a leaving group:
Claims
exact text as granted — not AI-modified1 ) A process for the preparation of a compound of formula (IA) or (IB) below:
comprising reacting a compound of formula (IIa) or (IIb) respectively
in the presence of 31 OR, wherein R in the case of formation of compound (IA) is CH 2 CH 3 and R in the case of formation of compound (IB) is CH 2 CH 2 CH 3 , and wherein X is a leaving group:
2 ) A process as claimed in claim 1 wherein X is selected from the group consisting of arylsulphonyloxy, C 1 -C 4 alkylsulphonyloxy, nitro or halo substituted benzenesulphonyloxy, C 1 -C 4 perfluoroalkylsulphonyloxy, aroyloxy, substituted aroyloxy, C 1 -C 4 perfluoroalkanoyloxy, C 1 -C 4 alkanoyloxy, halo; diazonium; C 1 -C 4 primary and secondary alkoxy, oxonium, perchloryloxy, quatenaryammonium C 1 -C 4 alkylsulphonuloxy, halosulphonyloxy, halonium and diarylsulphonylamino.
3 ) A process as claimed in claim 2 wherein X is a halo or methoxy.
4 ) A process as claimed in claim 3 wherein X is fluoro, chloro or methoxy.
5 ) A process as claimed in claim 4 wherein X is fluoro or chloro.
6 ) A process as claimed in claim 1 wherein − OR is present with an auxiliary base.
7 ) A process as claimed in claim 6 wherein the auxiliary base is selected from the group consisting of sterically hindered base, a metal salt of 1-methyl piperazine, 1-ethylpiperazine, morpholine, a metal hydride, metal oxide, metal carbonate and metal bicarbonate.
8 ) A process as claimed in claim 7 wherein the sterically hindered base is a metal salt of a sterically hindered alcohol or amine.
9 ) A process as claimed in claim 8 wherein the metal salt of a sterically hindered alcohol or amine is selected from the group consisting of a secondary or tertiary C 4 -C 12 alkanol, a C 3 -C 12 cycloalkanol and a secondary or tertiary (C 3 -C 8 cycloalkyl)C 1 -C 6 alkanol, a N-(secondary or tertiary C 3 -C 6 alkyl)-N-(primary, secondary or tertiary C 3 -C 6 alkyl)amine, a N-(C 3 -C 8 cycloalkyl)-N-(primary, secondary or tertiary C 3 -C 6 alkyl)amine, a di(C 3 -C 8 cycloalkyl)amine or hexamethyldisilazane 1,5-diazabicyclo[4,3,0]non-5-ene 1,8-diazabicyclo[5,4,0]undec-7-ene and a tertiary amine.
10 ) A process as claimed in claim 9 wherein the auxiliary base is a metal salt of a tertiary alkanol.
11 ) A process as claimed in claim 1 wherein the reaction is carried out in an inert solvent or ROH or a mixture of an inert solvent and ROH.
12 ) A process as claimed in claim 11 wherein the solvent is selected from the group consisting of ethanol, n-propanol, a secondary or tertiary C 4 -C 12 alkanol, a C 3 -C 12 cycloalkanol, a tertiary C 4 -C 12 cycloalkanol, a secondary or tertiary (C 3 -C 7 cycloalkyl)C 2 -C 6 alkanol, a C 3 -C 9 alkanone, 1,2-dimethoxyethane, 1,2-diethoxyethane, diglyme, tetrahydrofuran, 1,4-dioxan, toluene, xylene, chlorobenzene, 1,2-dichlorobenzene, acetonitrile, dimethyl sulphoxide, sulpholane, dimethylformamide, N-methylpyrrolidin-2-one, pyridine, and mixtures thereof.
13 ) A process as claimed in claim 12 wherein the solvent is selected from the group consisting of ethanol, n-propanol, a tertiary C 4 -C 12 alkanol, a tertiary C 4 -C 12 cycloalkanol, a tertiary (C 3 -C 7 cycloalkyl)C 2 -C 6 alkanol, a C 3 -C 9 alkanone, 1,2-dimethoxyethane, 1,2-diethoxyethane, diglyme, tetrahydrofuran, 1,4-dioxan, toluene, xylene, chlorobenzene, 1,2-dichlorobenzene, acetonitrile, sulpholane, dimethylformamide, N-methylpyrrolidin-2-one, pyridine, and mixtures thereof.
14 ) A process as claimed in claim 13 wherein the solvent is ethanol or propanol.
15 ) A process for the preparation of a compound of formula (IA) or (IB) below:
comprising reacting a compound of formula (IIA) or (IIB) respectively
in the presence of − OR, wherein R in the case of formation of compound (IA) is CH 2 CH 3 and R in the case of formation of compound (IB) is CH 2 CH 2 CH 3 , or − OR together with an auxiliary base or ZOR together with an auxiliary base wherein ZOR is a salt of − OR and Z is a cation.
16 ) A process as claimed in claim 15 for the production of compound (IA)
comprising reacting compound (IIA):
a) with ethanol and auxiliary base, optionally in an inert solvent; or
b) with ZOEt and an auxiliary base in ethanol or an inert solvent or a mixture thereof; or
c) with ZOEt and ethanol or an inert solvent or a mixture thereof wherein Z is a cation.
17 ) A process as claimed in claim 15 for the production of compound (IB)
comprising reacting compound (IIB):
a) with propanol and an auxiliary base, optionally in an inert solvent; or
b) with ZOPr and an auxiliary base, in propanol or an inert solvent or a mixture of both; or
c) with ZOPr, and propanol or an inert solvent or a mixture of both wherein Z is a cation.
18 ) A process as claimed in claim 16 wherein the compound of formula (IIA) is prepared by coupling a compound of formula (VIIA)
with a compound of formula (IXA)
19 ) A process as claimed in claim 17 wherein a compound of formula (IIB) is prepared by coupling a compound of formula (VIIB)
with a compound of formula (IXB)
20 ) A process as claimed in claim 18 wherein a compound of the formula (VIIA) is formed by coupling a compound of formula (VIA) with N-methylpiperazine
21 ) A process as claimed in claim 19 wherein a compound of formula (VIIB) is formed by coupling a compound of formula (VIA) with N-ethylpiperazine.
22 ) A compound of formula (IIA) or (IIB):
wherein X is a leaving group.
23 ) A compound of formula (IIIA) or (IIIB):
wherein X is a leaving group.
24 ) A compound of formula (VIIA) or (VIIB)
wherein X is a leaving group.
25 ) A compound according to claim 22 wherein X is selected from the group consisting of fluoro, chloro and methoxy.
26 ) A compound according to claim 23 wherein X is selected from the group consisting of fluoro, chloro and methoxy.
27 ) A compound according to claim 24 wherein X is selected from the group consisting of fluoro, chloro and methoxy.Cited by (0)
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