Dimethyl Sulfoxide → N-[(1R)-2-Hydroxy-1-phenylethyl]-10-[(2'-methoxy-1,1'-biphenyl-4-YL)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamide

HRID 639205노트

반응식

HRID 639205 반응식
ClC(Cl)(Cl)[C:3]([C:5]1[N:14]2[C:8]([CH2:9][N:10]([C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[O:33][CH3:34])=[CH:23][CH:22]=3)=[O:20])[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13]2)=[CH:7][CH:6]=1)=[O:4].[NH2:37][C@H:38]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH2:39][OH:40].CS(C)=O.C(N(CC)CC)C>C(#N)C.ClCCl>[OH:40][CH2:39][C@H:38]([NH:37][C:3]([C:5]1[N:14]2[C:8]([CH2:9][N:10]([C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[O:33][CH3:34])=[CH:23][CH:22]=3)=[O:20])[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13]2)=[CH:7][CH:6]=1)=[O:4])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

참가 물질

7

반응물 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 2724025(R)-beta-aminophenethyl alcoholHCID 160384072,2,2-trichloro-1-{10-[(2'-methoxy-1,1'-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone

생성물 1

HCID 16038410N-[(1R)-2-Hydroxy-1-phenylethyl]-10-[(2'-methoxy-1,1'-biphenyl-4-YL)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-C][1,4]benzodiazepine-3-carboxamide수율 51.5%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

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온도
82.5 °C

실험 절차

A mixture of 2,2,2-trichloro-1-{10-[(2′-methoxy-1,1′-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone of Example 1 (0.517 g, 0.985 mmole) and (R)-(−)-2-amino-2-phenylethanol (0.276 g, 20 mmole), dimethylsulfoxide (2.8 mmole) and triethylamine (0.213 g, 2.1 mmole) in acetonitrile (10 mL) was heated at 80-85° C. for 22 hours. The residue left upon removal of the solvent was taken up in 15 mL of dichloromethane, washed with brine, dried over anhydrous magnesium sulfate and concentrated to give a tan solid. Purification by flash chromatography on silica gel Merck-60 using a gradient of 0 to 25% ethyl acetate in dichloromethane provided a light yellow solid (0.283 g). Recrystallization from ethyl acetate/hexane gave the title compound as off-white needles, m.p. 195-196° C. MS [(+)ESI, m/z]: 558.14 [M+H]+

후처리

  1. waitThe residue left upon removal of the solvent
  2. washwashed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customto give a tan solid
  6. customPurification by flash chromatography on silica gel Merck-60

출처 및 근거

ORD 기록
ord-621b7f1e320746a683cbb8d9cff1ab17
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07691848B2

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