Ethyl Acetate → 3(R)-t-Butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-[[(benzyloxycarbonyl)amino]methyl][1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-2-one

HRID 1740261노트

반응식

HRID 1740261 반응식
[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:15][CH2:14][C:13]2[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=2[N:11]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH2:33][NH2:34])=[CH:23][CH:22]=2)[C:10]1=[O:35])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:36]([O:43][C:44](ON1C(=O)CCC1=O)=[O:45])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.ON1C2C=CC=CC=2N=N1.C(OCC)(=O)C>C(Cl)Cl.C(N(CC)CC)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[CH2:15][CH2:14][C:13]2[CH:16]=[CH:17][CH:18]=[CH:19][C:12]=2[N:11]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[CH2:33][NH:34][C:44]([O:43][CH2:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)=[O:45])=[CH:25][CH:26]=2)[C:10]1=[O:35])=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

7

반응물 4

HCID 8857Ethyl AcetateHCID 757711-HydroxybenzotriazoleHCID 83172Benzyl succinimido carbonateHCID 228774603(R)-t-Butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-aminomethyl[1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-2-one

생성물 1

HCID 228774613(R)-t-Butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-[[(benzyloxycarbonyl)amino]methyl][1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-2-one수율 83%

시약·촉매·용매 2

HCID 8471Triethylamine촉매HCID 6344Dichloromethane용매

실험 절차

A solution of 64 mg (0.14 mmol) of 3(R)-t-butoxycarbonylamino-2,3,4,5-tetrahydro-1-[[2'-aminomethyl[1,1'-biphenyl]-4-yl]methyl]-1H-benzazepin-2-one (Example 59, Step C) in 1 mL of methylene chloride at room temperature was treated with 1 drop of triethylamine followed by 36 mg (0.14 mmol, 1 eq.) of N-(benzyloxycarbonyloxy)succinimide and 5 mg of N-hydroxybenzotriazole. The mixture was stirred at room temperature for 1 hour then added to 10 mL of ethyl acetate and washed with 5% aqueous citric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The organic layer was removed, dried over magnesium sulfate, filtered and solvents removed under vacuum. The residue was purified by medium pressure liquid chromatography on silica, eluting with ethyl acetate/hexanes (2:1), to give 68 mg (0.11 mmol, 83%) of the product as a white, crusty foam. 1H NMR (400 MHz, CDCl3): δ 1.38 (s, 9H), 1.89 (m, 1H), 2.40-2.60 (m, 3H), 4.27 (m, 3H), 4.75 (br t, 1H), 4.92 (d, 15 Hz, 1H), 5.05 (s, 2H), 5.18 (d, 15 Hz, 1H), 5.44 (br d, 7 Hz, 1H), 7.10-7.35 (m, 11H), 7.40 (d, 8 Hz, 1H). FAB-MS: calculated for C37H39N3O5 605; found 606 (M+H, 2%), 506 (M-BOC, 100%).

후처리

  1. washwashed with 5% aqueous citric acid, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  2. customThe organic layer was removed
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customsolvents removed under vacuum
  6. customThe residue was purified by medium pressure liquid chromatography on silica
  7. washeluting with ethyl acetate/hexanes (2:1)

출처 및 근거

ORD 기록
ord-f7dd40b19fe8415784de91ae57105ed3
출처 데이터셋
uspto-grants-1999_10
특허 번호
US05968924

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