Diisopropylethylamine → (2r)-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 2184438노트

반응식

HRID 2184438 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]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 6973630(-)-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 10122056(2r)-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

반응 조건

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 Example 5, 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 (S)-(−)-glycidol (0.10 mL, 1.51 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 (0.36 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-0c900d71396a45549af18913332c2e55
출처 데이터셋
uspto-grants-2005_05
특허 번호
US06900200B2

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