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 30304ノート

反応式

HRID 30304 の反応式
[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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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-Hydroxy-benzotriazole 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).

後処理

  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

出典と根拠

ORDレコード
ord-c244e8262bfd41bdaf615b58baed7684
出典データセット
uspto-grants-2008_09
特許番号
US07423033B2

反応ノート

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