Chlorine → 2-{(S)-2-[(E)-3-(5-chloro-2-tetrazol-1-yl-phenyl)-acryloylamino]-3-phenyl-propionylamino}-thiazole-5-carboxylic acid

HRID 384606Notes

Reaction equation

[Li+].[OH-:2].C1[CH2:7][O:6]CC1.O.C(OC([C:14]1[N:15]=[C:16]([NH:19][C:20](=[O:46])[C@@H:21]([NH:29][C:30](=[O:45])/[CH:31]=[CH:32]/[C:33]2[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=2[N:40]2[CH:44]=[N:43][N:42]=[N:41]2)[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[S:17][CH:18]=1)=O)C.ClCl>>[Cl:39][C:37]1[CH:36]=[CH:35][C:34]([N:40]2[CH:44]=[N:43][N:42]=[N:41]2)=[C:33](/[CH:32]=[CH:31]/[C:30]([NH:29][C@@H:21]([CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20]([NH:19][C:16]2[S:17][C:18]([C:7]([OH:6])=[O:2])=[CH:14][N:15]=2)=[O:46])=[O:45])[CH:38]=1

Participants

Reactant 3

HCID 24526Chlorine

HCID 594019392-{(S)-2-[(E)-3-(5-chloro-2-tetrazol-1-yl-phenyl)-acryloylamino]-3-phenyl-propionylamino}-thiazole-4-carboxylic acid ethyl ester

HCID 66916791HCID 66916791, compound

Product 1

HCID 251672252-{(S)-2-[(E)-3-(5-chloro-2-tetrazol-1-yl-phenyl)-acryloylamino]-3-phenyl-propionylamino}-thiazole-5-carboxylic acid

Procedure

LiOH/THF/water hydrolysis of 2-{(S)-2-[(E)-3-(5-chloro-2-tetrazol-1-yl-phenyl)-acryloylamino]-3-phenyl-propionylamino}-thiazole-4-carboxylic acid ethyl ester (Example 18) afforded Example 22. HPLC purity: >97%. LCMS m/z 524.3 (M+H, chlorine isotope). 1H NMR (400 MHz, CD3OD) δ: 9.49 (s, 1H), 7.96 (ds, 2H), 7.72-7.54 (m, 2H), 7.27 (m, 5H), 7.10 (d, J=15.7 Hz, 1H), 6.75 (d, J=15.7 Hz, 1H), 4.90 (m, 1H), 3.27 (m, 1H), 3.11 (m, 1H) ppm. Analytical HPLC RT: 5.58 min (Method C, 8 min gradient).

Workup

customafforded Example 22
customAnalytical HPLC RT: 5.58 min (Method C, 8 min gradient)

Sources & evidence

ORD record: ord-56c1685bacdd43abbe34b074106b6f06
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367709B2

Reaction notes

Loading…