Granted Patent B2

US 7,855,291 · App. 11/647,517 · Granted Dec 21, 2010

Abstract

Claims (44)

1. A method of preparing a compound of formula I(a):

which comprises contacting a compound of formula II:

with a compound of formula III:

under conditions sufficient for the formation of the compound of formula I(a), wherein:

A is optionally substituted cycloalkyl, aryl, or heterocycle;

X is O, S, or NR 6 ;

Y 1 is halogen;

P 1 is R 1 or a protecting group;

P 2 is a protecting group;

P 3 is OR 2 , SR 2 , NR 9 R 10 , or NHNHR 9 ;

R 1 is hydrogen or optionally substituted alkyl, alkyl-aryl, alkyl-heterocycle, aryl, or heterocycle;

R 2 is hydrogen or optionally substituted alkyl, alkyl-aryl, alkyl-heterocycle, aryl, or heterocycle;

R 3 is hydrogen, cyano, or optionally substituted alkyl or aryl;

R 4 is hydrogen, cyano, or optionally substituted alkyl or aryl;

R 6 is hydrogen or optionally substituted alkyl or aryl;

R 7 is independently hydrogen, cyano, nitro, halogen, OR 8 , NR 9 R 10 , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;

each R 8 is independently hydrogen or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;

each R 9 is independently hydrogen, a protecting group, or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;

each R 10 is independently hydrogen, a protecting group, or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle; and

n is 1-4.

2. The method of claim 1 , wherein the compound of formula II is of formula II(a):

wherein:

each R 11 is independently hydrogen, cyano, nitro, halogen, OR 8 , NR 9 R 10 , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;

each R 12 is independently hydrogen, cyano, nitro, halogen, OR 8 , NR 9 R 10 , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;

m is 1-5; and

p is 1-4.

3. The method of claim 2 , wherein the compound of formula II(a) is of formula II(b):

4. The method of claim 1 , which further comprises deprotecting the compound of formula I(a) to provide a compound of formula I:

5. The method of claim 4 , wherein the compound of formula I is of formula I(b):

wherein:

each R 11 is independently hydrogen, cyano, nitro, halogen, OR 8 , NR 9 R 10 , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;

each R 12 is independently hydrogen, cyano, nitro, halogen, OR 8 , NR 9 R 10 , or optionally substituted alkyl, alkyl-aryl or alkyl-heterocycle;

m is 1-5; and

p is 1-4.

6. The method of claim 5 , wherein the compound of formula I(b) is of formula I(c):

7. The method of claim 6 , wherein the compound of formula I(c) is of formula I(d):

8. The method of claim 6 , wherein the compound of formula I(d) is of formula I(e):

9. A compound of the formula:

or a salt or solvate thereof, wherein:

P 1 is R 1 , aryl-alkyl, heteroaryl-alkyl, or —C(O)R 13 ;

P 2 is aryl-alkyl, heteroaryl-alkyl, or —C(O)R 13 ;

R 1 is hydrogen or optionally substituted alkyl, alkyl-aryl, alkyl-heterocycle, aryl, or heterocycle; and

each R 13 is independently alkyl, aryl-alkyl, aryl, heterocycle, alkoxy, aryloxy, or aryl-alkoxy.

10. The compound of claim 9 , which is of the formula:

Assignments (12)