Diisopropylethylamine → (2S)-2-([N-methyl-N-{(1R)-1-(N-methyl-N-[(1R)-1-(methylcarbamoyl)-2-phenylethyl]carbamoyl)-2-(2-naphthyl)ethyl}carbamoyl]methoxymethyl)pyrrolidine-1-carboxylic acid tert-butylester

HRID 366250노트

반응식

HRID 366250 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][CH2:15][C:16]([OH:18])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.[CH3:41][N:42]([C@@H:59]([C:67](=[O:70])[NH:68][CH3:69])[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)CC)(C)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][O:14][CH2:15][C:16](=[O:18])[N:56]([CH3:57])[C@@H:44]([C:43](=[O:58])[N:42]([CH3:41])[C@@H:59]([C:67](=[O:70])[NH:68][CH3:69])[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)=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9931019(2R)-N-methyl-2-methylamino-N-((1R)-1-(methylcarbamoyl)-2-phenylethyl)-3-(2-naphthyl)propionamideHCID 10682697(S)-2-Carboxymethoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 70007448(2S)-2-([N-methyl-N-{(1R)-1-(N-methyl-N-[(1R)-1-(methylcarbamoyl)-2-phenylethyl]carbamoyl)-2-(2-naphthyl)ethyl}carbamoyl]methoxymethyl)pyrrolidine-1-carboxylic acid tert-butylester수율 78.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (2S)-2-(((carboxy)methoxy)methyl)-pyrrolidin-1-carboxylic acid tert-butylester (1.2 g, 4.5 mmol) in dichloromethane (20 ml) were added 1-hydroxy-7-azabenzotriazole (612 mg, 4.5 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (950 mg, 4.95 mmol) and the mixture was stirred for 30 min. (2R)-N-Methyl-2-methylamino-N-((1R)-1-(methylcarbamoyl)-2-phenylethyl)-3-(2-naphthyl)propionamide (605 mg, 1.5 mmol) in dichloromethane (10 mL) was added followed by diisopropylethylamine (0.33 ml, 2.0 mmol) and the mixture was stirred for 2 hours at room temperature. The mixture was washed with water (10 ml), aqueous sodium bicarbonate (10 ml), water (2×10 ml), brine (10 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed on silica (40 g) with ethyl acetate/heptane 4:1 to give 760 mg of (2S)-2-([N-methyl-N-{(1R)-1-(N-methyl-N-[(1R)-1-(methylcarbamoyl)-2-phenylethyl]carbamoyl)-2-(2-naphthyl)ethyl}carbamoyl]methoxymethyl)pyrrolidine-1-carboxylic acid tert-butylester. The obtained product was taken up in 50% trifluoroacetic acid in methylene chloride (5 ml) and stirred for 10 min. Then saturated sodium bicarbonate was added until pH 8 and the phases were separated. The aqueous phase was extracted with dichloromethane (2×10 ml) and the combined organic phases were washed with brine (5 ml), dried over magnesium sulfate and concentrated in vacuo. The product was redissolved in water (30 ml) and acetic s acid (2 ml) was added and the mixture was liophilized to give 720 mg of the acetate salt of the title compound as an amorphous powder.

후처리

  1. additionwas added
  2. washThe mixture was washed with water (10 ml), aqueous sodium bicarbonate (10 ml), water (2×10 ml), brine (10 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was chromatographed on silica (40 g) with ethyl acetate/heptane 4:1

출처 및 근거

ORD 기록
ord-ef72205792964e2c9a18ac7588b64975
출처 데이터셋
uspto-grants-2000_10
특허 번호
US06127391

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