PROCESSES FOR THE PREPARATION OF (S)-TERT-BUTYL 4,5-DIAMINO-5-OXOPENTANOATE

• US 20190084924A1
• Filed: 08/20/2018
• Published: 03/21/2019
• Est. Priority Date: 08/21/2017
• Status: Active Grant

• Current Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Original Assignee: Celgene Corporation (Bristol-Myers Squibb Company)
• Inventors: Traverse, John F., Zacuto, Michael J., Zhang, Weihong, Johnson, Kirsten Faye, Geherty, Maryll E., Marton, Christopher
• Granted Patent: US 10,717,703 B2
• Time in Patent Office: Days
• CPC Class Codes: C07C 231/02 from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
• CPC Class Codes: C07C 231/12 by reactions not involving the formation of carboxamide groups
• CPC Class Codes: C07C 231/18 by stereospecific synthesis
• CPC Class Codes: C07C 237/06 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 237/12 having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups peptides C07K
• CPC Class Codes: C07C 273/1809 with formation of the N-C(O)-N moiety
• CPC Class Codes: C07C 275/06 of an acyclic and saturated carbon skeleton
• CPC Class Codes: C07C 275/24 containing six-membered aromatic rings
• CPC Class Codes: C07C 275/70 Compounds containing any of the groups , e.g. isoureas
• CPC Class Codes: C07C 67/313 by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups
• CPC Class Codes: C07C 69/84 of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring
• CPC Class Codes: C07D 209/46 with an oxygen atom in position 1
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Provided are processes for the preparation of (S)-tert-butyl 4,5-diamino-5-oxopentanoate, or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof. Also provided are solid forms of various intermediates and products obtained from the processes.

Claims

1. A process for preparing a compound of Formula (I):

5. The process of claim 1, wherein the compound of Formula (II), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, is prepared by a process comprising (x) contacting a compound of Formula:

6. The process of claim 5, wherein the formaldehyde source is paraformaldehyde or 1,3,5-trioxane.

7. The process of claim 5, wherein step (x) occurs in the presence of an acid.

8. The process of claim 7, wherein the acid is p-TsOH, MsOH, benzenesulfonic acid, trifluoromethanesulfonic acid, trifluoroacetic acid, sulfuric acid, or trichloroacetic acid.

9. The process of claim 1, wherein R² is hydrogen.

10. The process of claim 9, wherein the NH₂—

R² (i.e., NH₃) in step (a) is provided in the form of an ammonia solution in water or MeOH or in the form of gaseous ammonia.

11. The process of claim 1, wherein R² is a suitable amino protecting group.

12. The process of claim 11, wherein the deprotection of the —

NH—

R¹ group and the deprotection of the —

NH—

R² group in step (c) are conducted separately.

13. The process of claim 11, wherein the deprotection of the —

NH—

R¹ group and the deprotection of the —

NH—

R² group in step (c) are conducted simultaneously.

14. The process of claim 11, wherein R² is benzyl, 4-methoxybenzyl, or 3,4-dimethoxybenzyl.

15. The process of claim 11, wherein R² is (S)-1-phenylethyl.

16. The process of claim 1, wherein R¹ is benzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, benzyloxycarbonyl, or p-methoxybenzyloxycarbonyl.

17. The process of claim 16, wherein R¹ is benzyloxycarbonyl.

18. The process of claim 1, wherein step (b) occurs in the presence of t-butyl 2,2,2-trichloroacetimidate.

19. The process of claim 1, wherein step (b) occurs in the presence of O-t-Bu-DIC isourea.

20. The process of claim 19, wherein the O-t-Bu-DIC isourea is formed by reacting diisopropylcarbodiimide (DIC) with t-butanol and a Cu(I) salt in the presence of oxygen.

21. The process of claim 20, wherein the oxygen is present in an amount of up to about 22%, from about 1% to about 10%, from about 2% to about 6%, or about 4% of the atmosphere.

22. The process of claim 1, wherein step (c) occurs under a hydrogenation condition.

23. The process of claim 1, wherein the compound is converted to a hydrochloride salt of the compound in step (d).

2. A process for preparing a compound of Formula (I):

3. The process of claim 2, wherein the compound of Formula (IV), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, is prepared by a process comprising

(b) transforming a compound of Formula (III):

4. The process of claim 3, wherein the compound of Formula (III), or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, is prepared by a process comprising

(a) contacting a compound of Formula (II):

24. A process for preparing a compound of Formula (I):

25-33. -33. (canceled)

34. A process for preparing a compound of Formula (I):

35. A process for preparing a compound of Formula (I):

36-41. -41. (canceled)

42. A process for preparing a compound of Formula (I-rac):

43. A process for preparing a compound of Formula (I-rac):

44-62. -62. (canceled)

63. A process for preparing a compound of Formula (I-rac):

64-71. -71. (canceled)

72. A process for preparing a compound of Formula (XIV):

73-90. -90. (canceled)

91. A process for preparing a compound of Formula (XV):

92-100. -100. (canceled)

101. A solid form, which is Form A of Compound 7, Form A of racemic Compound 7, Form A of Compound 8, Form A of racemic Compound 8, Form A of Compound 1, Form B of Compound 1, Form A of racemic Compound 1, Form A of Compound 35, Form 1 of Compound 37, or Form 1 of racemic Compound 37.

102-130. -130. (canceled)

131. A process for the preparation of O-t-Bu-DIC isourea of the structure:

132. (canceled)