Diisobutylaluminum hydride → 4-chloro-N-({4-chloro-3-[(3-chloro-5-methylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

HRID 1875150노트

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HRID 1875150 반응식
Br[C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:11]([F:35])=[C:12]([CH2:17][NH:18][C:19]([C:21]3[N:25]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH:24]=[N:23][C:22]=3[Cl:34])=[O:20])[CH:13]=[CH:14][C:15]=2[Cl:16])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:36]C(C[AlH]CC(C)C)C.C[Zn]C>C1COCC1.CCOC(C)=O>[Cl:34][C:22]1[N:23]=[CH:24][N:25]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:32])[CH3:33])[C:21]=1[C:19]([NH:18][CH2:17][C:12]1[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([O:9][C:4]2[CH:3]=[C:2]([CH3:36])[CH:7]=[C:6]([Cl:8])[CH:5]=2)[C:11]=1[F:35])=[O:20]

참가 물질

6

반응물 3

HCID 14487Diisobutylaluminum hydrideHCID 68487164N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamideHCID 178477796HCID 178477796, 화합물

생성물 1

HCID 684873244-chloro-N-({4-chloro-3-[(3-chloro-5-methylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide수율 744.4%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
60 °C

실험 절차

To a solution of N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (112 mg, 0.180 mmol) and 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) dichloromethane complex (7.33 mg, 8.98 μmol) in THF (5 ml) at 0° C. was added DIBAL-H (1.0 M solution in dichloromethane) (0.018 ml, 0.018 mmol), followed by dimethylzinc (1.0 M solution in heptane) (0.197 ml, 0.197 mmol), and the reaction mixture was stirred with heating at 60° C. for one hour. The 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-chloro-5-methylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (75 mg, 0.134 mmol, 75% yield). 1H NMR (400 MHz, DMSO-d5) δ ppm 8.72-8.86 (m, 1H), 7.98 (s, 1H), 7.45 (dd, J=8.6, 1.4 Hz, 1H), 7.30-7.40 (m, 1H), 7.01 (s, 1H), 6.71 (d, 2H), 5.49 (s, 2H), 4.47 (d, 2H), 3.38 (t, 2 H), 2.25 (s, 3H), 0.75 (t, 2H), −0.09 (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-a1bc0667a1dc44f68e9793ea3a5dbb59
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08304419B2

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