Diisopropylethylamine → 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(trifluoromethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

HRID 1875162Notes

Reaction equation

HRID 1875162 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:23])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[Cl:24][C:25]1[N:26]=[CH:27][N:28]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:29]=1[C:30](O)=[O:31].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.CCOC(C)=O>[Cl:24][C:25]1[N:26]=[CH:27][N:28]([CH2:33][O:34][CH2:35][CH2:36][Si:37]([CH3:40])([CH3:39])[CH3:38])[C:29]=1[C:30]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([O:10][C:11]2[CH:18]=[C:17]([C:19]([F:22])([F:20])[F:21])[CH:16]=[C:13]([C:14]#[N:15])[CH:12]=2)[C:4]=1[F:23])=[O:31]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 684835233-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(trifluoromethyl)benzonitrileHCID 684855334-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid

Product 1

HCID 866449424-chloro-N-[(4-chloro-3-{[3-cyano-5-(trifluoromethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamideYield 65.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(trifluoromethyl)benzonitrile (85.0 mg, 0.247 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (68.3 mg, 0.247 mmol) and HATU (94 mg, 0.247 mmol) in DMF (5 ml) was added diisopropylethyl amine (0.086 ml, 0.493 mmol) and the reaction mixture was stirred for 30 minutes at rt. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via silica gel chromatography to give 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(trifluoromethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (97 mg, 0.161 mmol, 65% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.74 (t, 1H), 8.09 (s, 1H), 7.95 (s, 1H), 7.74 (s, 1H), 7.70 (s, 1H), 7.43-7.53 (m, 1H), 7.39 (t, 1H), 5.47 (s, 2H), 4.46 (d, 2H), 3.35 (t, 2H), 0.59-0.81 (m, 2H), −0.12 (s, 9H).

Workup

  1. washwashed with water
  2. customThe solvent was removed
  3. customthe crude material was purified via silica gel chromatography

Sources & evidence

ORD record
ord-f690365ea4fb4640b20933d18ac1eb11
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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