2,6-Difluorobenzoyl isocyanate → N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl][[(2,6-difluorobenzoyl)amino]carbonyl]amino]thio]-L-proline, methyl ester

HRID 255609Notes

Reaction equation

HRID 255609 reaction equation
[F:1][C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([F:13])[C:3]=1[C:4]([N:6]=[C:7]=[O:8])=[O:5].[Cl:14][C:15]1[CH:39]=[C:38]([C:40]([F:43])([F:42])[F:41])[CH:37]=[CH:36][C:16]=1[O:17][C:18]1[CH:23]=[CH:22][C:21]([NH:24][S:25][N:26]2[CH2:34][CH2:33][CH2:32][C@H:27]2[C:28]([O:30][CH3:31])=[O:29])=[C:20]([F:35])[CH:19]=1>C1(C)C=CC=CC=1>[Cl:14][C:15]1[CH:39]=[C:38]([C:40]([F:43])([F:41])[F:42])[CH:37]=[CH:36][C:16]=1[O:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]([C:7]([NH:6][C:4](=[O:5])[C:3]2[C:2]([F:1])=[CH:12][CH:11]=[CH:10][C:9]=2[F:13])=[O:8])[S:25][N:26]2[CH2:34][CH2:33][CH2:32][C@H:27]2[C:28]([O:30][CH3:31])=[O:29])=[C:20]([F:35])[CH:19]=1

Participants

4

Reactant 2

HCID 27333692,6-Difluorobenzoyl isocyanateHCID 131714973N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl]amino]thio]-L-proline, methyl ester

Product 1

HCID 131715277N-[[[4-[2-chloro-4-(trifluoromethyl)phenoxy]-2-fluorophenyl][[(2,6-difluorobenzoyl)amino]carbonyl]amino]thio]-L-proline, methyl esterYield 60.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 2,6-difluorobenzoylisocyanate (2.8 g) in a 1:1 mixture of toluene and petroleum ether (10 ml) was added at room temperature over 30 minutes to a stirred solution of the compound of Example 4 (6.5 g) in the same solvent (20 ml). After stirring at room temperature for 3 hours, the solvent was stripped and the residue purified by chromatography over silica using dichloromethane as eluant, to give 5.5 g of the desired product, melting point 65°-68° C.

Workup

  1. customthe residue purified by chromatography over silica

Sources & evidence

ORD record
ord-f48bf99c4b884ac3901e95e8f0c1342c
Source dataset
uspto-grants-1987_10
Patent number
US04698365

Reaction notes

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