Triethylamine → 3-(2(R)-Cyclopentylmethyl-3 (S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one

HRID 1633478노트

반응식

HRID 1633478 반응식
[CH:1]1([CH2:6][C@H:7]([C@@H:11]([OH:20])[CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:32][CH:33]1[N:39]=[C:38]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C:37]2[CH:46]=[CH:47][CH:48]=[CH:49][C:36]=2[N:35]([CH3:50])[C:34]1=[O:51].O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl.C(OCC)(=O)C>[CH:1]1([CH2:6][C@H:7]([C@@H:11]([OH:20])[CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]([NH:32][CH:33]2[N:39]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:37]3[CH:46]=[CH:47][CH:48]=[CH:49][C:36]=3[N:35]([CH3:50])[C:34]2=[O:51])=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

참가 물질

7

반응물 4

HCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 183467692(R)-cyclopentylmethyl-3(S)-hydroxyl-5-phenylpentanoic acidHCID 219414933-Amino-1-methyl-5-phenyl-2,3-dihydro-1h-1,4-benzodiazepin-2-one p-toluenesulfonate salt

생성물 1

HCID 98930003-(2(R)-Cyclopentylmethyl-3 (S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

A mixture of acid 4 (250 mg, 0.900 mmol) and 3-amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one p-toluenesulfonate salt (364 mg, 0.820 mmol) in 4 mL of methylene chloride was stirred at 0° C. 1-Hydroxybenzotriazole hydrate (133 mg, 0.980 mmol), 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (314 mg, 1.64 mmol) and triethylamine (0.51 mL, 3.7 mmol) were added sequentially. After the mixture was stirred for 16 h, 30 mL of ethyl acetate was added. The organic layer was washed with 1 M HCl (15 mL), 5% NaHCO3 (30 mL) and brine (30 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification by chromatotron (30% ethyl acetate-hexane) afforded two diastereomers A and B. A: 120 mg (25%); 1H NMR (300 MHz, CDCl3) δ 7.20-7.70 (15H, m)), 5.54 (1H, d, J=8.0 Hz), 4.02 (1H, m), 3.48 (3H, s), 2.83-3.00 (1H, m), 2.62-2.74 (1H, m), 2.40-2.48 (1H, m), 1.00-2.00 (13H, m); MS (ESI): 524 (M+H), 546 (M+Na), 522 (M−H), 558 (M+Cl). B: 120 mg (25%); 1H NMR (300 MHz, CDCl3) δ 7.60 (1H, d, J=6.9 Hz), 7.20-7.45 (14H, m), 5.56 (1H, d, J=8.4 Hz), 3.84 (1H, m), 3.48 (3H, s), 2.83-3.00 (1H, m), 2.62-2.74 (1H, m), 2.50-2.60 (1H, m), 1.00-1.95 (13H, m); MS (ESI): 524 (M+H), 546 (M+Na), 522 (M−H).

후처리

  1. stirringAfter the mixture was stirred for 16 h
  2. washThe organic layer was washed with 1 M HCl (15 mL), 5% NaHCO3 (30 mL) and brine (30 mL)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customPurification by chromatotron (30% ethyl acetate-hexane)
  6. customafforded two diastereomers A and B

출처 및 근거

ORD 기록
ord-7ec8d50e6f674723b54e6b841aff556c
출처 데이터셋
uspto-grants-2003_01
특허 번호
US06503902B2

반응 노트

불러오는 중…