Triethylamine → 4-(1,3-Dioxo-1,3dihydrobenzo[f]isoindol-2-yl)-2-{1-[2-(4-methoxyphenyl)-1-(methylcarbamoyl)-ethylcarbamoyl]cyclohexylamino}butyric acid tert-butyl ester

HRID 1459895ノート

反応式

HRID 1459895 の反応式
[C:1]([O:5][C:6]([CH:8]([NH:26][C:27]1([C:33]([OH:35])=O)[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[CH2:9][CH2:10][N:11]1[C:19](=[O:20])[C:18]2[CH:17]=[C:16]3[CH:21]=[CH:22][CH:23]=[CH:24][C:15]3=[CH:14][C:13]=2[C:12]1=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C[NH-].[CH3:39][O:40][C:41]1[CH:52]=[CH:51][C:44]([CH2:45][C@@H:46]([C:48](O)=[O:49])[NH2:47])=[CH:43][CH:42]=1.O.O[N:55]1[C:59]2C=CC=CC=2N=N1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:1]([O:5][C:6](=[O:7])[CH:8]([NH:26][C:27]1([C:33](=[O:35])[NH:47][CH:46]([C:48](=[O:49])[NH:55][CH3:59])[CH2:45][C:44]2[CH:51]=[CH:52][C:41]([O:40][CH3:39])=[CH:42][CH:43]=2)[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]1)[CH2:9][CH2:10][N:11]1[C:12](=[O:25])[C:13]2[CH:14]=[C:15]3[CH:24]=[CH:23][CH:22]=[CH:21][C:16]3=[CH:17][C:18]=2[C:19]1=[O:20])([CH3:4])([CH3:3])[CH3:2]

参加物

7

反応物 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 700859441-[1-Tert-butoxycarbonyl-3-(1,3-dioxo-1,3-dihydrobenzo[f]isoindol-2-yl)propylamino]cyclohexanecarboxylic acidHCID 131721053L-tyrosine methyl ether N-methylamide hydrochloride

生成物 1

HCID 700834344-(1,3-Dioxo-1,3dihydrobenzo[f]isoindol-2-yl)-2-{1-[2-(4-methoxyphenyl)-1-(methylcarbamoyl)-ethylcarbamoyl]cyclohexylamino}butyric acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 1-[1-tert-butoxycarbonyl-3-(1,3-dioxo-1,3-dihydrobenzo[f]isoindol-2-yl)propylamino]cyclohexanecarboxylic acid (298 mg,0.62 mmol) in methylene chloride (10 mL) were added successively L-tyrosine methyl ether N-methylamide hydrochloride (180 mg, 0.74 mmol), 1-hydroxybenztriazole hydrate (95 mg, 0.62 mmol), triethylamine (0.12 mL, 0.86 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (142 mg, 0.74 mmol). The resulting mixture was stirred for 3 days at room temperature. After dilution with methylene chloride, the mixture was washed successively with saturated aqueous sodium bicarbonate, water, 0.5M aqueous hydrochloric acid and brine. The solution was dried over magnesium sulfate. The solvent was removed by evaporation under vacuum leaving an oil which was chromatographed on silica gel eluting with 45% hexane in ethyl acetate to afford 4-(1,3-dioxo-1,3dihydrobenzo[f]isoindol-2-yl)-2-{1-[2-(4-methoxyphenyl)-1-(methylcarbamoyl)-ethylcarbamoyl]cyclohexylamino}butyric acid tert-butyl ester, diastereomer A (91 mg, 22%) and diastereomer B (85 mg, 20%), in addition to a mixture of diastereomers A and B (169 mg, 41%).

後処理

  1. washAfter dilution with methylene chloride, the mixture was washed successively with saturated aqueous sodium bicarbonate, water, 0.5M aqueous hydrochloric acid and brine
  2. dry with materialThe solution was dried over magnesium sulfate
  3. customThe solvent was removed by evaporation under vacuum
  4. customleaving an oil which
  5. customwas chromatographed on silica gel eluting with 45% hexane in ethyl acetate

出典と根拠

ORDレコード
ord-4679a9c9e122419abd9eeff3fab7cdb4
出典データセット
uspto-grants-1998_12
特許番号
US05854275

反応ノート

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