US2002058823A1PendingUtilityA1
Preparation of cyclohexene carboxylate derivatives
Est. expiryAug 23, 2016(expired)· nominal 20-yr term from priority
Inventors:Kenneth M. KentChoung U. KimLawrence R. McgeeJohn D. Munger, Jr.Ernest J. PrisbeMichael J. PostichJohn C. RohloffDaphne E. KellyMatthew A. WilliamsLijun Zhang
C07D 317/46C07D 303/40C07C 227/08B05B 7/1209C07D 203/26C07C 2601/16Y02P20/55
48
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Claims
Abstract
The present invention provides new synthetic methods and compositions. In particular, new methods of preparing intermediates useful in the synthesis of neuraminidase inhibitors and compositions useful as intermediates that are themselves useful in the synthesis of neuraminidase inhibitors are provided.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A process for preparation of compounds of the formula:
wherein:
R 1 is a cyclic hydroxy protecting group;
R 2 is a carboxylic acid protecting group;
R 3 is a hydroxy protecting group; and
each R 20 is independently H or an alkyl of 1 to 12 carbon atoms;
which process comprises reaction of a compound of the formula:
with a dehydrating reagent.
2 . The process of claim 1 which further comprises separating compound 5 by treatment with a noble metal complex.
3 . The process of claim 1 wherein compound 4 is of the formula:
4 . A process for preparation of compounds of the formula:
wherein:
R 2 is a carboxylic acid protecting group;
R 3 is a hydroxy protecting group;
R 4 is —C(R 30 ) 3 ;
R 5 is H or R 3 ;
R 7 is H or an amino protecting group;
R8 is H or R 2 ;
R 9 is H or a thiol protecting group;
each R 20 is independently H or an alkyl of 1 to 12 carbon atoms;
each R 21 is independently R 2 , Br, Cl, F, I CN, NO 2 or N 3 ;
each R 22 is independently F, Cl, Br, I, CN, N 3 , —NO 2 , —OR 5 , —OR20, —N(R 20 ) 2 , —N(R 20 )(R 7 ), —N(R 7 ) 2 , —SR 20 , —SR 9 , —S(O)R 2 t, —S(O) 2 R 20 , —S(O)OR 20 ), —S(O)OR 8 , —S(O) 2 OR 20 , —S(O) 2 OR 8 , C(O)OR 20 , —C(O)OR 8 , OC(O)R 20 , —N(R 20 )(C(O)R 20 ), —N(R 7 )(C(O)R 20 , —N(R 20 )(C(O)OR 20 ), —N(R 7 )(C(O)OR 20 , —C(O)N(R 20 ) 2 , —C(O)N(R 7 )(R 20 ), —C(O)N(R 7 ) 2 , —C(NR 20 )(N(R 20 ) 2 ), —C(N(R 7 ))(N(R 20 ) 2 ), —C(N(R 20 ))(N(R 20 )(R 7 )), —C(N(R 7 ))(N(R 20 )(R 7 )), —C(N(R 20 ))(N(R 7 ) 2 ), —C(N(R 7 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C (N(R 20 )) (N(R 20 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 7 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 7 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 7 ) 2 ), =O, =S, =N(R 20 ), =N(R 7 ) or W;
R 23 is independently alkyl of 1 to 11 carbon atoms, alkenyl of 2 to 11 carbon atoms, or alkynyl of 2 to 11 carbon atoms;
R 24 is independently R 23 wherein each R 23 is substituted with 0 to 3 R 22 groups;
R 24 a is independently alkylene of 1 to 11 carbon atoms, alkenylene of 2 to 11 carbon atoms, or alkynylene of 2-11 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R 22 groups;
R 28 is independently alkyl of 1 to 12 carbon atoms, alkenyl of 2 to 12 carbon atoms, or alkynyl of 2 to 12 carbon atoms;
R 29 is independently R 22 or R 28 wherein each R 28 is substituted with 0 to 3R 22 groups;
each R 30 is independently H, R 24 , W or —R 24a W; and
W is carbocycle or heterocycle wherein any one of which carbocycle or heterocycle is substituted with 0 to 3 R 29 groups; which process comprises reaction of a compound of the formula:
wherein R 31 is a ketal or acetal, with a lewis acid reagent;
provided that R 4 , taken as a whole, contains:
0 to 3 W groups substituted with 0 to 3 R 29 groups; and, in addition,
1 to 12 carbon atoms substituted with 0 to 3 R 22 groups.
5 . The process of claim 4 which further comprises treating compound 10 with a reducing reagent.
6 . The process of claim 4 wherein compound 11 is of the formula;
7 . A process for preparation of compounds of the formula:
wherein:
R 2 is a carboxylic acid protecting group;
R 3 is a hydroxy protecting group;
R 4 is —C(R 30 ) 3 ;
R 5 is H or R 3 ;
R 7 is H or an amino protecting group;
R 8 is H or R 2 ;
R 9 is H or a thiol protecting group;
each R 20 is independently H or an alkyl of 1 to 12 carbon atoms;
each R 21 is independently R 20 , Br, Cl, F, I CN, NO 2 or N 3 ;
each R 22 is independently F, Cl, Br, I, —CN, N 3 , —NO 2 , —OR 5 , —OR 20 , —N(R 20 ) 2 , —N(R 20 )(R 7 ), —N(R 7 ) 2 , -SR 20 , -SR 9 , —S(O)R 20 , —S(O) 2 R 20 , —S(O)OR 20 , —S(O)OR 8 , —S(O) 2 OR 20 , —S(O) 2 OR 8 , C(o)OR 2 O, —C(O)OR 8 , —OC(O)R 20 , —N(R 20 )(C(O)R 20 ), —N(R 7 )(C(O)R 20 ), —N(R 20 )(C(O)OR 20 ), —N(R 7 )(C(O)OR 20 ), —C(O)N(R 20 ) 2 , —C(O)N(R 7 )(R 20 ), —C(O)N(R 7 ) 2 , —C(NR 20 )(N(R 20 ) 2 ), —C(N(R 7 ))(N(R 20 ) 2 ), —C(N(R 20 )) (N(R 20 )(R 7 )), —C(N(R 7 ))(N(R 20 )(R 7 )), —C(N(R 20 ))(N(R 7 ) 2 ), —C(N(R 7 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 20 )C(N(R 20 ) )(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 7 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 7 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 7 ) 2 ), =O, =S, =N(R 20 ), =N(R 7 ) or W;
R 23 is independently alkyl of 1 to 11 carbon atoms, alkenyl of 2 to 11 carbon atoms, or alkynyl of 2 to 11 carbon atoms;
R 24 is independently R 23 wherein each R 23 is substituted with 0 to 3 R 22 groups;
R 24 a is independently alkylene of 1 to 11 carbon atoms, alkenylene of 2 to 11 carbon atoms, or alkynylene of 2-11 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R 22 groups;
R 28 is independently alkyl of 1 to 12 carbon atoms, alkenyl of 2 to 12 carbon atoms, or alkynyl of 2 to 12 carbon atoms;
R 29 is independently R 22 or R 28 wherein each R 28 is substituted with 0 to 3 R 22 groups;
each R 30 is independently H, R 24 , W or —R 24a W;
W is carbocycle or heterocycle wherein any one of which carbocycle or heterocycle is substituted with 0 to 3 R 29 groups;
which process comprises reaction of a compound of the formula:
with a reducing reagent;
provided that R 4 , taken as a whole, contains:
0 to 3 W groups substituted with 0 to 3 R 29 groups; and, in addition,
1 to 12 carbon atoms substituted with 0 to 3 R 22 groups.
8 . The process of claim 7 wherein the reducing reagent is a trisubstituted phosphine reducing reagent.
9 . The process of claim 7 wherein compound 31 is of the formula:
10 . A process for preparation of compounds of the formula:
wherein:
R 2 is a carboxylic acid protecting group;
R 3 is a hydroxy protecting group;
R 4 is —C(R 30 ) 3 ;
R 5 is H or R 3 ;
R 7 is H or an amino protecting group;
R 8 is H or R 2 ;
R 9 is H or a thiol protecting group;
each R 20 is independently H or an alkyl of 1 to 12 carbon atoms;
each R 21 is independently R 20 , Br, Cl, F, I CN, NO 2 or N 3 ;
each R 22 is independently F, Cl, Br, I, —CN, N 3 , —NO 2 , —OR 5 , —OR 20 , —N(R 20 ) 2 , —N(R 20 )(R 7 ), —N(R 7 ) 2 , —SR 20 , —SR 9 , —S(O)R 20 , —S(O) 2 R 20 , —S(O)OR 20 , —S(O)OR 8 , —S(O) 2 OR 20 , —S(O) 2 OR 8 , —C(O)OR 20 , —C(O)OR 8 , —OC(O)R 20 , —N(R 20 )(C(O)R 20 ), —N(R 7 )(C(O)R 20 ), —N(R 20 )(C(O)OR 20 ), —N(R 7 )(C(O)OR 20 ), —C(O)N(R 20 ) 2 , —C(O)N(R 7 )(R 20 ), —C(O)N(R 7 ) 2 , —C(NR 20 )(N(R 20 ) 2 ), —C(N(R 7 ))(N(R 20 ) 2 ), —C(N(R 20 ))(N(R 20 )(R 7 )), —C(N(R 7 ))(N(R 20 )(R 7 )), —C (N(R 20 ) )(N(R 7 ) 2 ), —C (N(R 7 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 20 ) )(N(R 20 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 7 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 7 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 7 ) 2 ), =O, =S, =N(R 20 ), =N(R 7 ) or W;
R 23 is independently alkyl of 1 to 11 carbon atoms, alkenyl of 2 to 11 carbon atoms, or alkynyl of 2 to 11 carbon atoms;
R 24 is independently R 23 wherein each R 23 is substituted with 0 to 3 R 22 groups;
R 24a is independently alkylene of 1 to 11 carbon atoms, alkenylene of 2 to 11 carbon atoms, or alkynylene of 2-11 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R 22 groups;
R 28 is independently alkyl of 1 to 12 carbon atoms, alkenyl of 2 to 12 carbon atoms, or alkynyl of 2 to 12 carbon atoms;
R 29 is independently R 22 or R 28 wherein each R 28 is substituted with 0 to 3 R 22 groups;
each R 30 is independently H, R 24 , W or —R 24a W;
W is carbocycle or heterocycle wherein any one of which carbocycle or heterocycle is substituted with 0 to 3 R 29 groups; and
Y 1 is a mono-, di- or unsubstituted amino group;
which process comprises reaction of a compound of the formula:
with an amine reagent;
provided that R 4 , taken as a whole, contains:
0 to 3 W groups substituted with 0 to 3 R 29 groups; and, in addition,
1 to 12 carbon atoms substituted with 0 to 3 R 22 groups.
11 . The process of claim 10 wherein the amine reagent is a phthalimide reagent.
12 . The process of claim 10 wherein compound 41 is of the formula:
13 . A process for preparation of compounds of the formula:
wherein:
R 2 is a carboxylic acid protecting group;
R 3 is a hydroxy protecting group;
R 4 is —C(R 30 ) 3 ;
R 5 is H or R 3 ;
R 7 is H or an amino protecting group;
R 8 is H or R 2 ;
R 9 is H or a thiol protecting group;
each R 20 is independently H or an alkyl of 1 to 12 carbon atoms;
each R 21 is independently R 20 , Br, Cl, F, I CN, NO 2 or N 3 ;
each R 22 is independently F, Cl, Br, I, —CN, N 3 , —NO 2 , —OR 5 , —OR 20 , —N(R 20 ) 2 , —N(R 20 )(R 7 ), —N(R 7 ) 2 , —SR 20 , —SR 9 , —S(O)R 20 , —S(O) 2 R 20 , —S(O)OR 20 , —S(O)OR 8 , —S(O) 20 R 20 , —S(O) 2 OR 8 , —C(O)OR 20 , —C(O)OR 8 , —OC(O)R 20 , —N(R 20 )(C(O)R 20 ), —N(R 7 )(C(O)R 20 ), —N(R 20 )(C(O)OR 20 ), —N(R 7 )(C(O)OR 20 ), —C(O)N(R 20 ) 2 , —C(O)N(R 7 ) (R 20 ), —C(O)N(R 7 ) 2 , —C(NR 20 )(N(R 20 ) 2 ), —C(N(R 7 ))(N(R 20 ) 2 ), —C(N(R 20 ))(N(R 20 )(R 7 )), —C(N(R 7 ))(N(R 20 )(R 7 )), —C(N(R 20 ))(N(R 7 ) 2 ), —C(N(R 7 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 ) (R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 7 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 7 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 7 ) 2 ), =O, =S, =N(R 20 ), =N(R 7 ) or W;
R 23 is independently alkyl of 1 to 11 carbon atoms, alkenyl of 2 to 11 carbon atoms, or alkynyl of 2 to 11 carbon atoms;
R 24 is independently R 23 wherein each R 23 is substituted with 0 to 3 R 22 groups;
R 24a is independently alkylene of 1 to 11 carbon atoms, alkenylene of 2 to 11 carbon atoms, or alkynylene of 2-11 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R 22 groups;
R 28 is independently alkyl of 1 to 12 carbon atoms, alkenyl of 2 to 12 carbon atoms, or alkynyl of 2 to 12 carbon atoms;
R 29 is independently R 22 or R 28 wherein each R 28 is substituted with 0 to 3 R 22 groups;
each R 30 is independently H, R 24 , W or —R 24a W;
W is carbocycle or heterocycle wherein any one of which carbocycle or heterocycle is substituted with 0 to 3 R 29 groups; and
Y 1 is a mono-, di- or unsubstituted amino group;
which process comprises reaction of a compound of the formula:
with an oxidizing reagent;
provided that R 4 , taken as a whole, contains:
0 to 3 W groups substituted with 0 to 3 R 29 groups; and, in addition,
1 to 12 carbon atoms substituted with 0 to 3 R 22 groups.
14 . The process of claim 13 wherein compound 51 is of the formula:
15 . A process for preparation of a compound of the formula:
wherein:
R 2 is a carboxylic acid protecting group;
R 3 is a hydroxy protecting group;
R 4 is —C(R 30 ) 3 ;
R 5 is H or R 3 ;
R 7 is H or an amino protecting group;
R 8 is H or R 2 ;
R 9 is H or a thiol protecting group;
each R 20 is independently H or an alkyl of 1 to 12 carbon atoms;
each R 21 is independently R 20 1 Br, Cl, F, I CN, N0 2 or N 3 ;
each R 22 is independently F, Cl, Br, I, —CN, N 3 , —NO 2 , —OR 5 , CR 20 , —N(R 20 ) 2 , —N(R 20 )(R 7 ), —N(R 7 ) 2 , —SR 20 , -SR 9 , —S(O)R 20 , —S(O) 2 R 20 , —S(O)OR 20 , —S(O)OR 8 , —S(O) 2 OR 20 , —S(O) 2 OR 8 , —C(O)OR 20 , —C(O)OR 8 , —OC(O)R 20 , —N(R 20 )(C(O)R 20 ), —N(R 7 )(C(O)R 20 ), —N(R 20 )(C(O)OR 20 ), —N(R 7 )(C(O)OR 20 ), —C(O)N(R 20 ) 2 , —C(O)N(R 7 )(R 20 ), —C(O)N(R 7 ) 2 , —C(NR 20 )(N(R 20 ) 2 ), —C(N(R 7 )) (N(R 20 ) 2 ), —C(N(R 20 ))(N(R 20 )(R 7 )), —C(N(R 7 ))(N(R 20 )(R 7 )), —C(N(R 20 ))(N(R 7 ) 2 ), —C(N(R 7 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 7 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 7 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 7 ) 2 ), =0, =S, =N(R 20 ), =N(R 7 ) or W;
R23 is independently alkyl of 1 to 11 carbon atoms, alkenyl of 2 to 11 carbon atoms, or alkynyl of 2 to 11 carbon atoms;
R 24 is independently R 23 wherein each R 23 is substituted with 0 to 3 R 22 groups;
R 24a is independently alkylene of 1 to 11 carbon atoms, alkenylene of 2 to 11 carbon atoms, or alkynylene of 2-11 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R 22 groups;
R 28 is independently alkyl of 1 to 12 carbon atoms, alkenyl of 2 to 12 carbon atoms, or alkynyl of 2 to 12 carbon atoms;
R 29 is independently R 22 or R 28 wherein each R 28 is substituted with 0 to 3 R 22 groups;
each R 30 is independently H, R 24 , W or —R 24a W;
W is carbocycle or heterocycle wherein any one of which carbocycle or heterocycle is substituted with 0 to 3 R 29 groups; and
Y 1 is a mono-, di- or unsubstituted amino group;
which process comprises reaction of a compound of the formula:
with a base;
provided that R 4 , taken as a whole, contains:
0 to 3 W groups substituted with 0 to 3 R 29 groups; and, in addition,
1 to 12 carbon atoms substituted with 0 to 3 R 22 groups.
16 . The process of claim 15 wherein compound 61 is of the formula:
17 . A process for preparation of compounds of the formula:
wherein:
R 2 is a carboxylic acid protecting group;
R 3 is a hydroxy protecting group;
R 4 is —C(R 30 ) 3 ;
R 5 is H or R 3 ;
R 7 is H or an amino protecting group;
R 8 is H or R 2 ;
R 9 is H or a thiol protecting group;
each R 20 is independently H or an alkyl of 1 to 12 carbon atoms;
each R 21 is independently R 20 , Br, Cl, F, I CN, NO 2 or N 3 ;
each R 22 is independently F, Cl, Br, I, —CN, N 3 , —NO 2 , —OR 5 , —OR 20 , —N(R 2 ′) 2 , —N(R 20 )(R 7 ), —N(R7) 2 , —SR 20 , —SR 9 , —S(O)R 20 , —S(O) 2 R 20 , —S(O)OR 20 , —S(O)OR 8 , —S(O) 2 OR 20 , —S(O) 2 OR 8 , —C(O)OR 20 , —C(O)OR 8 , OC(O)R 20 , —N(R 20 )(C(O)R 20 ), —N(R 7 )(C(O)R 20 ), —N(R 20 )(C(O)OR 20 ), —N(R 7 )(C(O)OR 20 ), —C(O)N(R 20 ) 2 , —C(O)N(R 7 )(R 20 ), —C(O)N(R 7 ) 2 , —C(NR 20 )(N(R 20 ) 2 ), —C(N(R 7 ))(N(R 20 ) 2 ), —C(N(R 20 )) (N(R 20 )(R 7 )), —C(N(R 7 ))(N(R 20 )(R 7 )), —C(N(R 20 ))(N(R 7 ) 2 ), —C(N(R 7 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 20 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 ) 2 ), —N(R 7 )C(N(R 20 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 20 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 20 )(R 7 )), —N(R 7 )C(N(R 20 ))(N(R 7 ) 2 ), —N(R 20 )C(N(R 7 ))(N(R 7 ) 2 ), —N(R 7 )C(N(R 7 ))(N(R 7 ) 2 ), =O, =S, =N(R 20 ), =N(R 7 ) or W;
R 23 is independently alkyl of 1 to 11 carbon atoms, alkenyl of 2 to 11 carbon atoms, or alkynyl of 2 to 11 carbon atoms;
R 24 is independently R 23 wherein each R 23 is substituted with 0 to 3 R 22 groups;
R 24a is independently alkylene of 1 to 11 carbon atoms, alkenylene of 2 to 11 carbon atoms, or alkynylene of 2-11 carbon atoms any one of which alkylene, alkenylene or alkynylene is substituted with 0-3 R 22 groups;
R 28 is independently alkyl of 1 to 12 carbon atoms, alkenyl of 2 to 12 carbon atoms, or alkynyl of 2 to 12 carbon atoms;
R 29 is independently R 22 or R 28 wherein each R 28 is substituted with 0 to 3 R 22 groups;
each R 30 is independently H, R 24 , W or —R 24a W;
W is carbocycle or heterocycle wherein any one of which carbocycle or heterocycle is substituted with 0 to 3 R 29 groups; and
Y 1 is a mono-, di- or unsubstituted amino group;
which process comprises reaction of a compound of the formula:
with a reductive amination reagent;
provided that R 4 , taken as a whole, contains:
0 to 3 W groups substituted with 0 to 3 R 29 groups; and, in addition,
1 to 12 carbon atoms substituted with 0 to 3 R 22 groups.
18 . The process of claim 17 wherein compound 71 is of the formula:
19 . A process according to any one or sequential combination of processes AA, AB, AC, AD, AE, AF, AG, AH, AL, AJ, or AK of Schemes 1 and2.
20 . A process according to any one or sequential combination of the processes of Example 1, Example 2, Example 3, Example 4 , Example 5, Example 6, Example 7, Example 8, Example 9, Example 10, Example 11, Example 12 or Example 13.
21 . A process according to any one or sequential combination of processes AL, AM, AN, AO, or AP of Scheme 3.
22 . A process for preparation of compounds of the formula:
wherein:
R 1 is a cyclic hydroxy protecting group;
R 2 is a carboxylic acid protecting group;
R 3 is a hydroxy protecting group; and
each R 20 is independently H or an alkyl of 1 to 12 carbon atoms;
which process comprises reaction of a compound of the formula:
with a dehydrating reagent;
provided that excluded is the process of converting a compound of the formula:
to a compound of the formula:
by reaction with POCl 3 in pyridine.
23 . The process of claim 22 wherein compound 4 is of the formula:
24 . A process for the preparation of a compound of the formula:
which process comprises reaction of a compound of the formula:
with a dehydrating reagent and a noble metal complex.
25 . A process for the preparation of a compound of the formula:
which process comprises reaction of a compound of the formula:
with a Lewis acid reagent.
26 . A process for the preparation of a compound of the formula:
wherein R is a mono-, di- or unsubstituted amino group,
which process comprises reaction of a compound of the formula:
with an amine reagent.
27 . A compound of the formula:
28 . A compound of the formula:
29 . A compound of the formula:
30 . A compound of the formula:
31 . A compound of the formula:
32 . A compound of the formula:
33 . A compound of the formula:
34 . A compound of the formula:
35 . A compound of the formula:
36 . A process for preparing the compound of the formula 116
which comprises
a) converting the compound of formula 110
to the compound of formula 111:
b) converting the compound of formula 111 to the compound of formula 113:
c) converting the compound of formula 113 to the compound of formula 114:
d) converting the compound of formula 114 to the compound of formula 115:
e) converting the compound of formula 115 to the compound of formula 116.
37 . The process of claim 36 wherein
a) in step a) compound 110 is treated with sodium azide;
b) in step b) compound 111 is treated with a reducing reagent, in particular triphenylphosphine;
c) in step c) compound 113 is treated with sodium azide;
d) in step d) compound 114 is treated with an acetylating reagent; and
e) in step e) compound 115 is subjected to catalytic hydrogenation.
38 . A process for preparing the compound of formula 116:
which comprises
a) converting the compound of formula 201
to the compound of formula 202
b) converting the compound of formula 202 to the compound of formula 203
c) converting the compound of formula 203 to the compound of formula 204
d) converting the compound of formula 204 to the compound of formula 205
e) converting the compound of formula 205 to the compound of formula 116.
39 . The process of claim 38 wherein
a) in step a) compound 201 is treated with an amine reagent;
b) in step b) compound 202 is treated with an oxidizing reagent;
c) in step c) compound 203 is treated with a base:
d) in step d) compound 204 is treated with a reductive amination reagent; and
e) in step e) compound 205 is treated with an acetylating reagent.Cited by (0)
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