Diisopropylethylamine → N-((1R)-1-(N-(2-(2-(methylsulfonylamino)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl-ester

HRID 650825

反応式

HRID 650825 の反応式
[C:1]([O:5][C:6]([N:8]([C@H:10]([CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)[C:11](O)=[O:12])[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:47][NH:48][CH2:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=1[NH:57][S:58]([CH3:61])(=[O:60])=[O:59].C(N(C(C)C)C(C)C)C>CN(C)C=O.ClCCl.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[N:8]([C@@H:10]([C:11](=[O:12])[N:48]([CH2:49][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=1[NH:57][S:58]([CH3:61])(=[O:60])=[O:59])[CH3:47])[CH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=1)[CH3:9])([CH3:2])([CH3:3])[CH3:4]

参加物

9

反応物 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10065151(2R)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-naphthalen-2-ylpropanoic acidHCID 10561338N-(2-(2-(methylamino)ethyl)phenyl)methanesulfonamide

生成物 1

HCID 53661815N-((1R)-1-(N-(2-(2-(methylsulfonylamino)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl-ester収率 33.6%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

(2R)-2-(N-(tert-Butoxycarbonyl)-N-methylamino)-3(2-naphthyl)propionic acid (444 mg, 1.35 mmol) and successively 1-hydroxy-7-azabenzotriazole (184 mg, 1.35 mmol) were dissolved in N,N-dimethylformamide (5 ml) and dichloromethane (7 ml). The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (259 mg, 1.35 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of N-(2-(2-(methylamino)ethyl)phenyl)methanesulfonamide (308 mg, 1.35 mmol) was added. Ethyldiisopropylamine (0.23 ml, 1.35 mmol) was added. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate and washed with 10% aqueous sodium hydrogen sulfate solution (70 ml). The aqueous phase was extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (150 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (60 g), using ethyl acetate/heptane (1:1) as eluent, to give 245 mg of N-((1R)-1-(N-(2-(2-(methylsulfonylamino)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl-ester.

後処理

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with 10% aqueous sodium hydrogen sulfate solution (70 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×50 ml)
  5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (150 ml)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customThe crude product was purified by flash chromatography on silica (60 g)

出典と根拠

ORDレコード
ord-93e3caaecaaa407eb0421790d6c2671b
出典データセット
uspto-grants-2001_08
特許番号
US06274584B1

関連ノート

読み込み中…