Pyridine → N-(4-Trifluoromethoxy-phenyl)-2-{2,6-dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]-phenylamino}-6-[3,3-difluoro-pyrrolidinyl]-1-methyl-1H-benzimidazole-5-carboxylic acid amide

HRID 1189651Notes

Reaction equation

HRID 1189651 reaction equation
[Cl:1][C:2]1[C:7]([CH2:8][NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:6][CH:5]=[C:4]([Cl:16])[C:3]=1[NH:17][C:18]1[N:22]([CH3:23])[C:21]2[CH:24]=[C:25]([N:31]3[CH2:35][CH2:34][C:33]([F:37])([F:36])[CH2:32]3)[C:26]([C:28]([OH:30])=O)=[CH:27][C:20]=2[N:19]=1.ClC(N(C)C)=C(C)C.[F:46][C:47]([F:57])([F:56])[O:48][C:49]1[CH:55]=[CH:54][C:52]([NH2:53])=[CH:51][CH:50]=1.N1C=CC=CC=1>CC#N.C(Cl)Cl>[F:46][C:47]([F:56])([F:57])[O:48][C:49]1[CH:50]=[CH:51][C:52]([NH:53][C:28]([C:26]2[C:25]([N:31]3[CH2:35][CH2:34][C:33]([F:36])([F:37])[CH2:32]3)=[CH:24][C:21]3[N:22]([CH3:23])[C:18]([NH:17][C:3]4[C:4]([Cl:16])=[CH:5][CH:6]=[C:7]([CH2:8][NH:9][C:10](=[O:15])[C:11]([CH3:14])([CH3:12])[CH3:13])[C:2]=4[Cl:1])=[N:19][C:20]=3[CH:27]=2)=[O:30])=[CH:54][CH:55]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 6008484-(Trifluoromethoxy)anilineHCID 6407921-Chloro-N,N-2-trimethylpropenylamineHCID 679572792-{2,6-Dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]-phenylamino}-6-[3,3-difluoro-pyrrolidinyl]-1-methyl-1H-benzimidazole-5-carboxylic acid

Product 1

HCID 57524633N-(4-Trifluoromethoxy-phenyl)-2-{2,6-dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]-phenylamino}-6-[3,3-difluoro-pyrrolidinyl]-1-methyl-1H-benzimidazole-5-carboxylic acid amide

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2-{2,6-dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]-phenylamino}-6-[3,3-difluoro-pyrrolidinyl]-1-methyl-1H-benzimidazole-5-carboxylic acid (50 mg, 0.090 mmol), (1-chloro-2-methyl-propenyl)-dimethylamine (0.026 mL, 0.20 mmol) and DCM (2 mL) is stirred for 30 min. This mixture is added to 4-trifluoromethoxyaniline (0.100 mmol) and pyridine (25 μL, 0.32 mmol) in MeCN (1 mL) and it is stirred for 2 h at 40° C. and overnight at 60° C. The mixture is concentrated and the residue diluted with DMF/water 19/1 (2 mL) and purified via reverse phase HPLC.

Workup

  1. stirringis stirred for 2 h at 40° C. and overnight at 60° C
  2. concentrationThe mixture is concentrated
  3. additionthe residue diluted with DMF/water 19/1 (2 mL)
  4. custompurified via reverse phase HPLC

Sources & evidence

ORD record
ord-1d6a3337b60049ebad738a60e927b959
Source dataset
uspto-grants-2014_03
Patent number
US08674113B2

Reaction notes

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