4-Isothiocyanato-2-(trifluoromethyl)benzonitrile → 4-(1-(4-cyano-3-(trifluoromethyl)phenylcarbamoyl)cyclopropylamino)-2-fluoro-N-methylbenzamide

HRID 570611Notes

Reaction equation

HRID 570611 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2([C:15]([OH:17])=O)[CH2:14][CH2:13]2)=[CH:7][C:6]=1[F:18])=[O:4].[F:19][C:20]([F:33])([F:32])[C:21]1[CH:28]=[C:27]([N:29]=C=S)[CH:26]=[CH:25][C:22]=1[C:23]#[N:24]>>[C:23]([C:22]1[CH:25]=[CH:26][C:27]([NH:29][C:15]([C:12]2([NH:11][C:8]3[CH:9]=[CH:10][C:5]([C:3]([NH:2][CH3:1])=[O:4])=[C:6]([F:18])[CH:7]=3)[CH2:13][CH2:14]2)=[O:17])=[CH:28][C:21]=1[C:20]([F:19])([F:32])[F:33])#[N:24]

Participants

3

Reactant 2

HCID 116155404-Isothiocyanato-2-(trifluoromethyl)benzonitrileHCID 671074031-(4-(Methylcarbamoyl)-3-fluorophenylamino)cyclopropanecarboxylic acid

Product 1

HCID 513493354-(1-(4-cyano-3-(trifluoromethyl)phenylcarbamoyl)cyclopropylamino)-2-fluoro-N-methylbenzamideYield 12%

Conditions

Temperature
140 °C

Procedure

A mixture of 1-(4-(methylcarbamoyl)-3-fluorophenylamino)cyclopropanecarboxylic acid (200 mg, 0.79 mmol) and 2-(trifluoromethyl)-4-isothiocyanatobenzonitrile (270 mg, 1.18 mmol) was heated at 140° C. for 3 h. The crude product was purified by silica gel chromatography (100-200 mesh silica, 5% acetone in DCM as eluant) to get 40 mg of 4-(1-(4-cyano-3-(trifluoromethyl)phenylcarbamoyl)cyclopropylamino)-2-fluoro-N-methylbenzamide, M+1: 421.

Workup

  1. customThe crude product was purified by silica gel chromatography (100-200 mesh silica, 5% acetone in DCM as eluant)

Sources & evidence

ORD record
ord-b49832cc72be44e5b5cd068d2d577693
Source dataset
uspto-grants-2015_05
Patent number
US09023869B2

Reaction notes

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