Ethyl orthoformate → (S)-2-phenyl-3-(1-(thiazolo[5,4-b]pyridin-7-ylamino)ethyl)-8-(trifluoromethyl)isoquinolin-1(2H)-one

HRID 869475Notes

Reaction equation

[NH2:1][C:2]1[C:3]([SH:32])=[N:4][CH:5]=[CH:6][C:7]=1[NH:8][C@H:9]([C:11]1[N:12]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:13](=[O:25])[C:14]2[C:19]([CH:20]=1)=[CH:18][CH:17]=[CH:16][C:15]=2[C:21]([F:24])([F:23])[F:22])[CH3:10].[CH:33](OCC)(OCC)OCC>>[C:26]1([N:12]2[C:11]([C@@H:9]([NH:8][C:7]3[CH:6]=[CH:5][N:4]=[C:3]4[S:32][CH:33]=[N:1][C:2]=34)[CH3:10])=[CH:20][C:19]3[C:14](=[C:15]([C:21]([F:23])([F:22])[F:24])[CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:25])[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

Reactant 2

HCID 31214Ethyl orthoformate

HCID 178461849HCID 178461849, compound

Product 1

HCID 71232778(S)-2-phenyl-3-(1-(thiazolo[5,4-b]pyridin-7-ylamino)ethyl)-8-(trifluoromethyl)isoquinolin-1(2H)-one

Procedure

A mixture of (S)-3-(1-(3-amino-2-mercaptopyridin-4-ylamino)ethyl)-2-phenyl-8-(trifluoro methyl)isoquinolin-1(2H)-one III-35 (80 mg, 0.175 mmol, 1.0 eq) in triethyl orthoformate (180 mL) was stirred at reflux for 2 h. The reaction mixture was allowed to cool to RT and then concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (1-2% MeOH-DCM) to afford the product, (S)-2-phenyl-3-(1-(thiazolo[5,4-b]pyridin-7-ylamino)ethyl)-8-(trifluoromethyl)isoquinolin-1(2H)-one III-36. ESI-MS m/z: 467.0 [M+H]+.

Workup

temperatureat reflux for 2 h
concentrationconcentrated in vacuo
customThe residue was purified by flash column chromatography on silica gel (1-2% MeOH-DCM)

Sources & evidence

ORD record: ord-d483d9562fba42bf94ce08f038f9b185
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969363B2

Reaction notes

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