HOAt → HCID 69740563、化合物

HRID 1268624ノート

反応式

HRID 1268624 の反応式
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]([CH3:27])([CH3:26])[CH2:20]/[CH:21]=[CH:22]/[C:23](O)=[O:24])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN(C)C(=O)[C@H](NC)CC1C=CC=CC=1.[CH3:65][N:66]([CH3:95])[C:67]([C@H:69]([N:77]([CH3:94])[C:78](=[O:93])[CH:79]([NH:91][CH3:92])[CH2:80][C:81]1[CH:90]=[CH:89][C:88]2[C:83](=[CH:84][CH:85]=[CH:86][CH:87]=2)[CH:82]=1)[CH2:70][C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1)=[O:68]>ClCCl>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:17])[NH:18][C:19]([CH3:26])([CH3:27])[CH2:20]/[CH:21]=[CH:22]/[C:23](=[O:24])[N:91]([C@@H:79]([C:78](=[O:93])[N:77]([C@@H:69]([C:67](=[O:68])[N:66]([CH3:65])[CH3:95])[CH2:70][C:71]3[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=3)[CH3:94])[CH2:80][C:81]3[CH:90]=[CH:89][C:88]4[C:83](=[CH:84][CH:85]=[CH:86][CH:87]=4)[CH:82]=3)[CH3:92])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

参加物

7

反応物 5

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22326974HCID 22326974、化合物HCID 54419464HCID 54419464、化合物HCID 86587343HCID 86587343、化合物

生成物 1

HCID 69740563HCID 69740563、化合物収率 68.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (2E)-5-(((9H-flouren-9-yl)methoxy)- carbonylamino)-5-methylhex-2-enoic acid (280 mg, 0.77 mmol) in dichloromethane (5 ml) were added 1-hydroxy-7-azabenzotriazole (126 mg, 0.92 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (207 mg, 1.08 mmol) and the mixture was stirred for 30 min. Then 2R)-N-((1R)-1-dimethylcarbamoyl-2-phenylethyl)-N-methyl-2-methylamino-3-(2-naphthyl)propionamide (386 mg, 0.92 mmol) in dichloromethane (5 ml) and diisoprbpylethylamine (0.17 ml, 1.00 mmol) were added and the mixture was stirred overnight at room temperature. The mixture was washed with water (20 ml), saturated aqueous sodium bicarbonate (20 ml), water (2×20 ml), brine (20 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed on silica (400 g) with ethyl acetate/heptan 1:1 to give 401 mg of ((3E)-4-(N-((1R)-1-(N-((1R)-1-dimethylcarbamoyl-2-phenylethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamoyl)-1,1-dimethylbut-3-enyl)carbamic acid 9H-flouren-9-ylmethyl ester. The obtained product was dissolved in 20% piperidine in dimethylformamide (10 ml) and stirred for 30 min. The mixture was chromatographed on silica (20 g) with dichloromethane/methanol/ammonia 89:10:1 to give 228 mg of (2E)-5-amino-5-methylhex-2-enoic acid N-((1R)-1-(N-((1R)-1-(dimethylcarbamoyl)-2-phenylethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylamide as an oil. The product was redissolved in water (30 ml) and acetic acid (2 ml) was added and the mixture was lyophilized to give 645 mg of the acetate salt of the title compound as an amorphous powder.

後処理

  1. stirringthe mixture was stirred overnight at room temperature
  2. washThe mixture was washed with water (20 ml), saturated aqueous sodium bicarbonate (20 ml), water (2×20 ml), brine (20 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was chromatographed on silica (400 g) with ethyl acetate/heptan 1:1

出典と根拠

ORDレコード
ord-2d80dfcd34ed49b4bdef90580bf064db
出典データセット
uspto-grants-2003_04
特許番号
US06555570B2

反応ノート

読み込み中…