Triethylamine → 2-[4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-2-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydro-1H-imidazol-1-YL]carbonyl]-1-piperazinyl]-1-(4-morpholinyl)ethanone

HRID 2425602

반응식

HRID 2425602 반응식
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:30](Cl)=[O:31])[C@H:13]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[C@H:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[N:15]=2)=[C:7]([O:33][CH2:34][CH3:35])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[N:43]1([C:49](=[O:57])[CH2:50][N:51]2[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>C(Cl)Cl>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:30]([N:54]3[CH2:53][CH2:52][N:51]([CH2:50][C:49]([N:43]4[CH2:44][CH2:45][O:46][CH2:47][CH2:48]4)=[O:57])[CH2:56][CH2:55]3)=[O:31])[C@H:13]([C:23]3[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=3)[C@H:14]([C:16]3[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=3)[N:15]=2)=[C:7]([O:33][CH2:34][CH3:35])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 1006221-(Morpholinocarbonylmethyl)piperazineHCID 57732375(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride

생성물 1

HCID 117218402-[4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-2-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydro-1H-imidazol-1-YL]carbonyl]-1-piperazinyl]-1-(4-morpholinyl)ethanone

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of (4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (7.967 g, 15.03 mmol, example 11) in methylene chloride (60 mL) cooled to 0° C. were added triethylamine (4.19 mL) and 1-morpholin-4-yl-2-piperazin-1-yl-ethanone (3.366 g, 15.78 mmol, Oakwood Products), respectively. The ice bath was removed, and the reaction mixture was stirred at room temperature for 30 min. The reaction was monitored by thin layer chromatography (silica gel, 20% ethyl acetate in hexane). The reaction mixture was concentrated to dryness, and the crude residue was purified by flash column chromatography (silica gel, eluting with 0.1% triethylamine in ethyl acetate) to give 2-{4-[(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone as white foam. The white foam was taken in 100 ml of ethyl acetate then filtered. Hydrogen chloride (18.04 mL, 1 M solution in diethyl ether) was added dropwise to the filtrate. The white solids formed were filtered off and dried in vacuo to give 2-{4-[(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone hydrochloride (9.3 g). HR-MS (ES, m/z) calculated for C38H46N5O4Cl2 [(M+H)+] 706.2922, observed 706.2917.

후처리

  1. customThe ice bath was removed
  2. concentrationThe reaction mixture was concentrated to dryness
  3. customthe crude residue was purified by flash column chromatography (silica gel, eluting with 0.1% triethylamine in ethyl acetate)

출처 및 근거

ORD 기록
ord-19ddfdef3544488b84091671a31c3607
출처 데이터셋
uspto-grants-2011_06
특허 번호
US07964724B2

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