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

HRID 1875165Notes

Reaction equation

HRID 1875165 reaction equation
[CH2:1]([C:5]1[CH:6]=[C:7]([O:12][C:13]2[C:14]([F:22])=[C:15]([CH2:20][NH2:21])[CH:16]=[CH:17][C:18]=2[Cl:19])[CH:8]=[C:9]([Cl:11])[CH:10]=1)[CH2:2][CH2:3][CH3:4].[Cl:23][C:24]1[N:25]=[CH:26][N:27]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:28]=1[C:29](O)=[O:30].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>[CH2:1]([C:5]1[CH:6]=[C:7]([O:12][C:13]2[C:14]([F:22])=[C:15]([CH2:20][NH:21][C:29]([C:28]3[N:27]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:38])([CH3:37])[CH3:39])[CH:26]=[N:25][C:24]=3[Cl:23])=[O:30])[CH:16]=[CH:17][C:18]=2[Cl:19])[CH:8]=[C:9]([Cl:11])[CH:10]=1)[CH2:2][CH2:3][CH3:4]

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 68485437({3-[(3-Butyl-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)amineHCID 684855334-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid

Product 1

HCID 68483744N-({3-[(3-butyl-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamideYield 82%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of ({3-[(3-butyl-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)amine (105 mg, 0.307 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (85 mg, 0.307 mmol) and HATU (117 mg, 0.307 mmol) in DMF (3 ml) was added diisopropylethyl amine (0.107 ml, 0.614 mmol) and the reaction mixture was stirred at rt for 45 minutes. 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 N-({3-[(3-butyl-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (151 mg, 0.251 mmol, 82% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.73 (t, 1H), 7.95 (s, 1H), 7.39-7.46 (m, 1H), 7.34 (t, 1H), 6.99 (s, 1H), 6.70 (s, 1H), 6.66 (s, 1H), 5.47 (s, 2H), 4.45 (d, 2H), 3.36 (t, 2H), 2.50 (t, 2H), 1.46 (t, 2H), 1.16-1.28 (m, 2H), 0.82 (t, 3 H), 0.73 (t, 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-c2cc08273ddd40869218871c372b4c52
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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