Processes for the preparation of (S)-tert-butyl 4,5-diamino-5-oxopentanoate

Patent metadata

Field	Value
Publication number	US-11912644-B2
Application number	US-202217978734-A
Country	US
Kind code	B2
Filing date	Nov 1, 2022
Priority date	Aug 21, 2017
Publication date	Feb 27, 2024
Grant date	Feb 27, 2024

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.

First claim

What is claimed is:

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

or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R 7 is hydrogen or a suitable hydroxyl protecting group, comprising
(a) contacting a compound of Formula (XV):

or an analog of a compound of Formula (XV) that contains an aldehyde-equivalent and/or carboxylic-equivalent group, or a solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, wherein R 8 is hydrogen, alkyl, or aryl, with a compound of Formula (I):

or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, to provide a compound of Formula (XIV), or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof; and
(b) optionally crystallizing the compound of Formula (XIV), or a salt, solvate, hydrate, enantiomer, mixture of enantiomers, or isotopologue thereof, from a solvent or mixture of solvents.

2. The process of claim 1 , wherein R 7 is hydrogen.

3. The process of claim 1 , wherein R 7 is a hydroxyl protecting group selected from the group consisting of allyl, methyl, 2-methoxyethoxymethyl (MEM), methoxymethyl (MOM), methoxythiomethyl, t-butoxymethyl, tri-isopropylsilyloxymethyl (TOM), ethyl, 1-ethoxyehtyl, isopropyl, t-butyl, benzyl, trityl (Tr), dimethoxytrityl (DMT), monomethoxytrityl (MMT), p-methoxybenzyl (PMB), acetyl, chloroacetyl, trichloroacetyl, trifluoroacetyl, pivaloyl (Piv), benzoyl, p-phenylbenzoyl, trimethylsilyl (TMS), triisopropylsilyl (TIPS), t-butyldimethylsilyl (TBDMS), and tetrahydropyranyl.

4. The process of claim 1 , wherein R 8 is alkyl.

5. The process of claim 4 , wherein R 8 is methyl.

6. The process of claim 1 , wherein the analog of a compound of Formula (XV) that contains an aldehyde-equivalent and/or carboxylic-equivalent group is a compound of the formula:

wherein:
each instance of R a is independently hydrogen, alkyl, aryl, acyl, or carbamoyl;
X is Cl, Br, OR b , SR c , SO 3 R c , or NR a R a ;
R b is hydrogen, alkyl, aryl, acyl, or silyl; and
R c is hydrogen, alkyl, or aryl.

7. The process of claim 1 , wherein step (a) is conducted with a salt of a compound of Formula (I) selected from a hydrochloride salt, a sulfonic acid salt, a phosphoric acid salt, an achiral carboxylic acid salt, and a chiral carboxylic acid salt.

8. The process of claim 7 , wherein step (a) is conducted with a hydrochloride salt of a compound of Formula (I).

9. The process of claim 1 , wherein step (a) occurs in the presence of a reducing reagent and optionally a base.

10. The process of claim 9 , wherein the reducing reagent is NaBH(OAc) 3 , NaBH 4 , NaBH 3 CN, silanes, or H 2 in combination with a transition metal catalyst.

11. The process of claim 10 , wherein the reducing reagent is NaBH(OAc) 3 .

12. The process of claim 9 , wherein the base is iPr 2 NEt, Et 3 N, n-Bu 3 N, DBU, or tetramethyl guanidine.

13. The process of claim 12 , wherein the base is iPr 2 Net.

14. The process of claim 1 , wherein step (a) occurs in a solvent selected from DMAc, MeOH, EtOH, trifluoroethanol, i-PrOH, 1-propanol, t-butanol, MeCN, DMF, NMP, THF, 2-MeTHF, DCM, and DCE, or a mixture thereof.

15. The process of claim 14 , wherein step (a) occurs in a solvent of DMAc.

16. The process of claim 1 , wherein the reaction temperature of step (a) is no more than about 5° C.

17. The process of claim 16 , wherein the reaction temperature of step (a) is from about 0° C. to about 5° C.

18. The process of claim 1 , wherein the crystallization of step (b) occurs in a solvent mixture of DMAc and water.

19. The process of claim 1 , wherein the crystallization of step (b) occurs in a solvent mixture of THF and heptanes.

Assignees

• Celgene Corp

Inventors

• Traverse John F
• Zacuto Michael J
• Zhang Weihong
• Johnson Kirsten Faye
• Geherty Maryll E
• Marton Christopher

Classifications

• C07C237/06

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• C07C269/06

  by reactions not involving the formation of carbamate groups · CPC title

• C07C231/12 Primary

  by reactions not involving the formation of carboxamide groups · CPC title

• C07C231/18 Primary

  by stereospecific synthesis · CPC title

• C07C67/313 Primary

  by introduction of doubly bound oxygen containing functional groups, e.g. carboxyl groups · CPC title