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Diisopropylethylamine → (2S)-3-{4-[(10-{[2-Methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)carbonyl]piperazin-1-yl}propane-1,2-diol

HRID 2184437
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HRID 2184437 반응식
Cl.[CH3:2][C:3]1[CH:8]=[C:7]([C:9]([N:11]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH2:15][N:14]3[C:22]([C:25]([N:27]4[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]4)=[O:26])=[CH:23][CH:24]=[C:13]3[CH2:12]2)=[O:10])[CH:6]=[CH:5][C:4]=1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[C:39]([F:42])([F:41])[F:40].C(N(CC)C(C)C)(C)C.[CH2:52]1[O:54][C@@H:53]1[CH2:55][OH:56]>CO>[CH3:2][C:3]1[CH:8]=[C:7]([C:9]([N:11]2[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=3[CH2:15][N:14]3[C:22]([C:25]([N:27]4[CH2:28][CH2:29][N:30]([CH2:52][C@H:53]([OH:54])[CH2:55][OH:56])[CH2:31][CH2:32]4)=[O:26])=[CH:23][CH:24]=[C:13]3[CH2:12]2)=[O:10])[CH:6]=[CH:5][C:4]=1[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[C:39]([F:40])([F:42])[F:41]
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참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 5460455(+)-GlycidolHCID 2194778410,11-Dihydro-10-[[2-methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl]-3-(1-piperazinylcarbonyl)-5h-pyrrolo[2,1-c][1,4]benzodiazepine hydrochloride salt

생성물 1

HCID 10145963(2S)-3-{4-[(10-{[2-Methyl-2'-trifluoromethyl-[1,1'-biphenyl]-4-yl]carbonyl}-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl)carbonyl]piperazin-1-yl}propane-1,2-diol

시약·촉매·용매

1
HCID 887Methanol용매

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온도
60 °C

실험 절차

To a solution of 10,11-dihydro-10-[[2-methyl-2′-trifluoromethyl-[1,1′-biphenyl]-4-yl]carbonyl]-3-(1-piperazinylcarbonyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine hydrochloride salt of Step B (0.50 g, 0.84 mmol) and N,N-diisopropylethyl amine (0.16 mL, 0.92 mmol) in methanol (5 mL) was added (R )-(+)-glycidol (0.10 mL, 1.50 mmol). The reaction mixture was heated to 60° C. for 4 hours then cooled and concentrated in vacuo. The residue was partitioned between dichloromethane and water. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a white foam. Purification by flash chromatography on silica gel using a solvent system of 5% methanol in chloroform provided the title product, which was redissolved in dichloromethane and evaporated to dryness in vacuo to a white foam (0.38 g).

후처리

  1. temperaturethen cooled
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between dichloromethane and water
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a white foam
  8. customPurification by flash chromatography on silica gel using a solvent system of 5% methanol in chloroform

출처 및 근거

ORD 기록
ord-2780a65511e44b3da22d6e4985e5d862
출처 데이터셋
uspto-grants-2005_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06900200B2

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