1-Hydroxybenzotriazole → (2S)-2-{[10-(4-Cyclohex-1-en-1-yl-3-methyl-benzoyl)-10,11-dihydro-5H-pyrrolo [2,1-c][1,4] benzodiazepine-3-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid ethyl ester

HRID 489581ノート

反応式

HRID 489581 の反応式
[C:1]1([C:7]2[CH:31]=[CH:30][C:10]([C:11]([N:13]3[C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=4[CH2:17][N:16]4[C:24]([C:27](O)=[O:28])=[CH:25][CH:26]=[C:15]4[CH2:14]3)=[O:12])=[CH:9][C:8]=2[CH3:32])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.Cl.[CH2:34]([O:36][C:37](=[O:48])[C@H:38]([CH2:40][C:41]1[CH:46]=[CH:45][C:44]([OH:47])=[CH:43][CH:42]=1)[NH2:39])[CH3:35].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=N)C.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C>[CH2:34]([O:36][C:37](=[O:48])[C@@H:38]([NH:39][C:27]([C:24]1[N:16]2[C:15]([CH2:14][N:13]([C:11](=[O:12])[C:10]3[CH:30]=[CH:31][C:7]([C:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=4)=[C:8]([CH3:32])[CH:9]=3)[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[CH2:17]2)=[CH:26][CH:25]=1)=[O:28])[CH2:40][C:41]1[CH:42]=[CH:43][C:44]([OH:47])=[CH:45][CH:46]=1)[CH3:35]

参加物

7

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2724939Tyrosine ethyl ester hydrochlorideHCID 10113257HCID 10113257、化合物HCID 21883477Ethylcarbodiimide hydrochloride

生成物 1

HCID 10189244(2S)-2-{[10-(4-Cyclohex-1-en-1-yl-3-methyl-benzoyl)-10,11-dihydro-5H-pyrrolo [2,1-c][1,4] benzodiazepine-3-carbonyl]-amino}-3-(4-hydroxy-phenyl)-propionic acid ethyl ester収率 59.5%

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

10-(4-Cyclohex-1-en-1-yl-3-methyl-benzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-3-carboxylic acid of Example 5, Step E (0.240 g, 0.563 mmol), L-tyrosine ethyl ester hydrochloride (0.157 g, 0.676 mmol), 1-hydroxy benzotriazole (0.084 g, 0.619 mmol) and 1-[3-dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (0.119 g, 0.619 mmol) were combined in amine-free N,N-dimethylformamide (2.25 mL), followed by the addition of N,N-diisopropylethylamine (0.294 mL, 1.69 mmol). The reaction was stirred at room temperature for 36 hours, then diluted with ethyl acetate and washed with water, 1 N hydrochloric acid, saturated aqueous sodium bicarbonate, and brine. The combined aqueous washings were saturated with sodium chloride and extracted with ethyl acetate. The combined organic phases were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash column chromatography on silica gel eluting with 50% ethyl acetate in hexane, followed by precipitation from diethyl ether with petroleum ether, to afford 0.207 g of the title compound as a white solid.

後処理

  1. washwashed with water, 1 N hydrochloric acid, saturated aqueous sodium bicarbonate, and brine
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic phases were dried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash column chromatography on silica gel eluting with 50% ethyl acetate in hexane
  7. customfollowed by precipitation from diethyl ether with petroleum ether

出典と根拠

ORDレコード
ord-bdfbd72242634727804148285715efbc
出典データセット
uspto-grants-2005_12
特許番号
US06977254B2

反応ノート

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