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 1875162노트

반응식

HRID 1875162 반응식
[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]

참가 물질

7

반응물 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

생성물 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-carboxamide수율 65.2%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-f690365ea4fb4640b20933d18ac1eb11
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08304419B2

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