Diisopropylethylamine → N-methyl-N-((3E)-4-(N-methyl-N-((1R)-1-(N-methyl-N-phenethylcarbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)-1,1-dimethylbut-3-enyl)carbamic acid tert-butyl ester

HRID 366125노트

반응식

HRID 366125 반응식
[C:1]([O:5][C:6]([N:8]([C:10]([CH3:18])([CH3:17])[CH2:11]/[CH:12]=[CH:13]/[C:14]([OH:16])=O)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:41][N:42]([CH2:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[C:43](=[O:58])[C@H:44]([NH:56][CH3:57])[CH2:45][C:46]1[CH:55]=[CH:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]=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:10]([CH3:18])([CH3:17])[CH2:11]/[CH:12]=[CH:13]/[C:14](=[O:16])[N:56]([CH3:57])[C@@H:44]([C:43](=[O:58])[N:42]([CH3:41])[CH2:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)[CH2:45][C:46]1[CH:55]=[CH:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]=1)([CH3:2])([CH3:3])[CH3:4]

참가 물질

9

반응물 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10593711(2R)-2-(methylamino)-3-(2-naphthyl)propionic acid N-methyl-N-phenethylamideHCID 10848750(2E)-5-(N-(tert-butoxycarbonyl)-N-methylamino)-5-methylhex-2-enoic acid

생성물 1

HCID 59965089N-methyl-N-((3E)-4-(N-methyl-N-((1R)-1-(N-methyl-N-phenethylcarbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)-1,1-dimethylbut-3-enyl)carbamic acid tert-butyl ester수율 72.6%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

(2E)-5-(N-(tert-Butoxycarbonyl)-N-methylamino)-5-methylhex-2-enoic acid (122 mg, 0.48 mmol) was dissolved in N,N-dimethylformamide (2 ml) and dichloromethane (2 ml). 1-Hydroxy-7-azabenzotriazole (65 mg, 0.48 mmol) was added. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (92 mg, 0.48 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of (2R)-2-(methylamino)-3-(2-naphthyl)propionic acid N-methyl-N-phenethylamide (165 mg, 0.48 mmol) in dichloromethane (2 ml) and ethyldiisopropylamine (0.083 ml, 0.48 mmol) were added successively. The solution was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (50 ml) and washed with 10% aqueous sodium hydrogen sulfate solution (50 ml). The aqueous phase was extracted with ethyl acetate (2×10 ml). The combined organic layers were washed with saturated aqueous sodium hydrogen carbonate solution (50 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (80 g), using ethyl acetate/heptane 1:1 as eluent to give 204 mg of N-methyl-N-((3E)-4-(N-methyl-N-((1R)-1-(N-methyl-N-phenethylcarbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)-1,1-dimethylbut-3-enyl)carbamic acid tert-butyl ester.

후처리

  1. stirringThe solution was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with 10% aqueous sodium hydrogen sulfate solution (50 ml)
  4. extractionThe aqueous phase was extracted with ethyl acetate (2×10 ml)
  5. washThe combined organic layers were washed with saturated aqueous sodium hydrogen carbonate solution (50 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 (80 g)

출처 및 근거

ORD 기록
ord-8f330155f62e422087b2c3cf1ea94ff5
출처 데이터셋
uspto-grants-2000_10
특허 번호
US06127354

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