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

HRID 384605Notes

Reaction equation

[Li+].[OH-].C1COCC1.O.C([O:11][C:12]([C:14]1[S:18][C:17]([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)=[N:16][CH:15]=1)=[O:13])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:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:20]([NH:19][C:17]2[S:18][C:14]([C:12]([OH:13])=[O:11])=[CH:15][N:16]=2)=[O:46])=[O:45])[CH:38]=1

Participants

Reactant 3

HCID 24526Chlorine

HCID 66916791HCID 66916791, compound

HCID 866432792-{(S)-2-[(E)-3-(5-chloro-2-tetrazol-1-yl-phenyl)-acryloylamino]-3-phenyl-propionylamino}-thiazole-5-carboxylic acid ethyl ester

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-5-carboxylic acid ethyl ester (Example 19) afforded Example 21. HPLC purity: >98%. LCMS m/z 524.2 (M+H, chlorine isotope). 1H NMR (400 MHz, CD3OD) δ: 9.48 (s, 1H), 8.02 (s, 1H), 7.96 (d, J=2.3 Hz, 1H), 7.68 (dd, J=2.3 & 9.2 Hz, 1H), 7.56 (d, J=8.5 Hz, 1H), 7.31-7.19 (m, 5H), 7.10 (d, J=15.7 Hz, 1H), 6.75 (d, J=15.6 Hz, 1H), 4.9 (t, 1H), 3.30 (m, 1H), 3.11 (m, 1H) ppm. Analytical HPLC RT: 5.48 min (Method C, 8 min gradient).

Workup

customafforded Example 21
customAnalytical HPLC RT: 5.48 min (Method C, 8 min gradient)

Sources & evidence

ORD record: ord-c24dc8d4ab534fd0b3b7668ce2aff35b
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367709B2

Reaction notes

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