Methods and intermediates for preparing pharmaceutical agents

Patent metadata

Field	Value
Publication number	US-2016002186-A1
Application number	US-201514799090-A
Country	US
Kind code	A1
Filing date	Jul 14, 2015
Priority date	Apr 3, 2009
Publication date	Jan 7, 2016
Grant date	—

Abstract

The invention provides methods and intermediates that are useful for preparing a compound of formula I:

and salts thereof.

First claim

1 - 8 . (canceled)

9 . A method for preparing a salt of a compound of formula XIV:

comprising treating a compound of formula XIV with an acid in an organic solvent.

10 . The method of claim 9 , wherein the acid is an organic acid.

11 . The method of claim 10 , wherein the organic acid is selected from the group consisting of oxalic acid, citric acid, and fumaric acid.

12 . The method of claim 9 , wherein the acid is oxalic acid.

13 . The method of claim 9 , wherein the organic solvent is selected from the group consisting of tert-butyl methyl ether, methylene chloride, tetrahydrofuran, acetone, acetonitrile, toluene, heptanes, isopropyl acetate, ethyl acetate, and an alcohol, and mixtures thereof.

14 . The method of claim 9 , wherein the organic solvent is acetone.

15 . The method of claim 9 , further comprising treating a compound of formula XIII:

or a salt thereof with morpholine to provide the compound of formula XIV.

16 . The method of claim 15 , further comprising treating a compound of formula XII:

or a salt thereof with a suitable iodide source to provide the compound of formula XIII or a salt thereof.

17 . The method of claim 9 , further comprising hydrolyzing the salt of the compound of formula XIV to provide a compound of formula Xa:

or a salt thereof.

18 . The method of claim 17 , wherein the compound of formula Xa is a salt and is of formula X:

wherein M + is K + .

19 . A method for preparing a salt of a compound of formula XIV:

comprising
a) treating a compound of formula XII:

or a salt thereof with a suitable iodide source to provide a compound of formula XIII:

or a salt thereof;
b) treating the compound of formula XIII or a salt thereof with morpholine to provide a compound of formula XIV:

and
(c) treating a compound of formula XIV with an acid in an organic solvent.

20 . The method of claim 19 , wherein the compound of formula XIII is used in step b) without purification from step a).

21 . The method of claim 19 , wherein the acid is an organic acid.

22 . The method of claim 21 , wherein the organic acid is selected from the group consisting of oxalic acid, citric acid, and fumaric acid.

23 . The method of claim 19 , wherein the acid is oxalic acid.

24 . The method of claim 19 , wherein the organic solvent is selected from the group consisting of tert-butyl methyl ether, methylene chloride, tetrahydrofuran, acetone, acetonitrile, toluene, heptanes, isopropyl acetate, ethyl acetate, and an alcohol, and mixtures thereof.

25 . The method of claim 19 , wherein the organic solvent is acetone.

26 . The method of claim 19 , further comprising hydrolyzing the salt of the compound of formula XIV to provide a compound of formula Xa:

or a salt thereof.

27 . The method of claim 26 , wherein the compound of formula Xa: is a salt and is of the formula X:

wherein M + is K + .

28 . An oxalate salt of a compound of formula XIV:

Assignees

• Gilead Sciences Inc

Inventors

• Polniaszek Richard
• Pfeiffer Steven
• Yu Richard
• Cullen Aaron
• Dowdy Eric
• Tran Duong
• Kent Kenneth
• Zhou Zhongxin
• Cordeau Douglas
• Easton-Scott Leah

Classifications

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07D417/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title