Trifluoroacetic acid → HCID 178454946, compound

HRID 1809985Notes

Reaction equation

[C:1](O)(C(F)(F)F)=[O:2].[Cl:8][C:9]1[CH:26]=[CH:25][CH:24]=[CH:23][C:10]=1[CH2:11][O:12][CH2:13][CH2:14][NH:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([CH3:22])[CH2:18][CH2:17]1.C([O:29][C:30](=[O:42])[C:31]([CH3:41])([CH3:40])[CH2:32][S:33][C:34]1[S:38][C:37]([NH2:39])=[N:36][CH:35]=1)C.C1N=CN(C(N2C=NC=C2)=O)C=1.[OH-].[Na+]>C1COCC1.CN(C1C=CN=CC=1)C.C(O)C>[Cl:8][C:9]1[CH:26]=[CH:25][CH:24]=[CH:23][C:10]=1[CH2:11][O:12][CH2:13][CH2:14][N:15]([C@H:16]1[CH2:17][CH2:18][C@H:19]([CH3:22])[CH2:20][CH2:21]1)[C:1](=[O:2])[NH:39][C:37]1[S:38][C:34]([S:33][CH2:32][C:31]([CH3:41])([CH3:40])[C:30]([OH:29])=[O:42])=[CH:35][N:36]=1

Participants

Conditions

Temperature: 75 °C

Procedure

The TFA salt of [2-(2-chloro-benzyloxy)-ethyl]-(trans-4-methyl-cyclohexyl)-amine (169 mg, 0.60 mmol) in THF (5 mL) was added 3-(2-amino-thiazol-5-ylsulfanyl)-2,2-dimethyl-propionic acid ethyl ester (195 mg, 0.75 mmol), CDI (243 mg, 1.50 mmol) and DMAP (3.7 mg, 0.03 mmol). The reaction mixture was stirred for 18 h. Ethanol (1 mL) and NaOH (2.5 N, 3 mL, 7.5 mmol) was added and the reaction mixture was heated to 75° C. for 5 h. The mixture was allowed to cool to rt before pH was adjusted (pH<1). The precipitate was filtered off and purified by preparative HPLC to give 170 mg (53%) of 3-{2-[3-[2-(2-Chloro-benzyloxy)-ethyl]-3-(trans-4-methyl-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-2,2-dimethyl-propionic acid.

Workup

temperatureto cool to rt before pH
filtrationThe precipitate was filtered off
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-f215cdf8b853440ea464de3488b02eee
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362049B2

Reaction notes

Loading…