Diisopropylethylamine → HCID 54455044, 화합물

HRID 365433

반응식

HRID 365433 반응식
Cl.CN(C)CCCN=C=NCC.[C:13]([O:17][C:18]([N:20]([C@H:22]([CH2:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=1)[C:23]([OH:25])=O)[CH3:21])=[O:19])([CH3:16])([CH3:15])[CH3:14].ON1C2N=CC=CC=2N=N1.[CH3:47][N:48]([CH3:73])[C:49](=[O:72])[C@@H:50]([NH:59][C:60](=[O:71])[C@H:61]([NH:69][CH3:70])[CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[CH2:51][CH2:52][CH2:53][CH2:54][NH:55][C:56](=[O:58])[CH3:57].C(N(C(C)C)C(C)C)C>ClCCl.CN(C)C=O.C(OCC)(=O)C>[C:13]([O:17][C:18](=[O:19])[N:20]([C@@H:22]([C:23](=[O:25])[N:69]([C@@H:61]([C:60](=[O:71])[NH:59][C@H:50]([C:49](=[O:72])[N:48]([CH3:47])[CH3:73])[CH2:51][CH2:52][CH2:53][CH2:54][NH:55][C:56](=[O:58])[CH3:57])[CH2:62][C:63]1[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=1)[CH3:70])[CH2:26][C:27]1[CH:28]=[CH:29][C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:36]=1)[CH3:21])([CH3:15])([CH3:14])[CH3:16]

참가 물질

9

반응물 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 54227586HCID 54227586, 화합물

생성물 1

HCID 54455044HCID 54455044, 화합물수율 73.6%

시약·촉매·용매 3

HCID 6228Dimethylformamide용매2회HCID 6344Dichloromethane용매2회HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (594 mg, 3.1 mmol) was added at 0° C. to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionic acid (1.02 g, 3.1 mmol) and 1-hydroxy-7-azabenzotriazole (422 mg, 3.1 mmol) in dichloromethane (10 ml) and N,N-dimethylformamide (5 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of the hydrochloride salt of crude (2S)-6-acetylamino-2-(((2R)-2-(methylamino)-3-phenylpropionyl)amino)hexanoic acid dimethylamide (1.28 g, 3.1 mmol) in dichloromethane (20 ml)and N,N-dimethylformamide (10 ml) and ethyidiisopropylamine (1.59 ml, 9.3 mmol) were added subsequently. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (200 ml) and washed with a 10% aqueous sodium hydrogen sulfate solution (150 ml). The aqueous solution was extracted wtih ethyl acetate (3×100 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (200 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (120 g), usin dichloromethane/methanol (10:1) as eluent, to give 1.57 g of N-((1R)-1-{N-[(1R)-1-((1S)-5-(acetylamino)-1-(dimethylcarbamoyl)pentylcarbamoyl)-2-phenylethyl]-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl ester.

후처리

  1. stirringThe reaction mixture was stirred for 16 h, while it
  2. temperaturewas warming up to room temperature
  3. washwashed with a 10% aqueous sodium hydrogen sulfate solution (150 ml)
  4. extractionThe aqueous solution was extracted wtih ethyl acetate (3×100 ml)
  5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (200 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 (120 g)

출처 및 근거

ORD 기록
ord-5d25af5a96eb4abeab81206a9f747040
출처 데이터셋
uspto-grants-2000_10
특허 번호
US06127341

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