N-Methyl-3-phenylpropan-1-amine → N-Methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester

HRID 650812

反応式

HRID 650812 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].Cl.CN(C)CCCN=C=NCC.[CH3:37][NH:38][CH2:39][CH2:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.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]([CH3:9])[C@@H:10]([C:11](=[O:12])[N:38]([CH3:37])[CH2:39][CH2:40][CH2:41][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[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)([CH3:2])([CH3:3])[CH3:4]

参加物

8

反応物 4

HCID 35417N-Methyl-3-phenylpropan-1-amineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10065151(2R)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-3-naphthalen-2-ylpropanoic acid

生成物 1

HCID 54207130N-Methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester収率 46.3%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回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 (2.21 g, 6.70 mmol) was dissolved in N,N-dimethylformamide (3 ml) and dichloromethane (6 ml). 1-Hydroxy-7-azabenzotrazole (0.91 g, 6.70 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.28 g, 6.70 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of N-methyl-N-(3-phenylpropyl)amine (1.0 g, 6.7 mmol) in dichloromethane (3 ml) was added. Ethyldiisopropylamine (1.2 ml, 6.7 mmol) was added. The reaction mixture was stirred for 16 h, while it was slowly warming up to room temperature. The solution was diluted with ethyl acetate (100 ml). It was washed with 1 N hydrochloric acid (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml) and dried over magnesium sulfate. Thesolvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetateiheptane (1:3) as eluent to give 1.43 g of N-methyl-N-((1R)-1-(N-methyl-N-(3-phenylpropyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamic acid tert-butyl ester.

後処理

  1. addition1-Hydroxy-7-azabenzotrazole (0.91 g, 6.70 mmol) was added
  2. stirringThe reaction mixture was stirred for 16 h, while it
  3. temperaturewas slowly warming up to room temperature
  4. washIt was washed with 1 N hydrochloric acid (100 ml)
  5. extractionThe aqueous phase was extracted with ethyl acetate (100 ml)
  6. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (100 ml)
  7. dry with materialdried over magnesium sulfate
  8. customThesolvent was removed in vacuo
  9. customThe crude product was purified by flash chromatography on silica (400 g)

出典と根拠

ORDレコード
ord-690a0a5c2f7f4a0a8d8d278ab3fc8a97
出典データセット
uspto-grants-2001_08
特許番号
US06274584B1

関連ノート

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