HOAt → HCID 69740563, 화합물

HRID 1268624노트

반응식

HRID 1268624 반응식
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C:19]([CH3:27])([CH3:26])[CH2:20]/[CH:21]=[CH:22]/[C:23](O)=[O:24])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN(C)C(=O)[C@H](NC)CC1C=CC=CC=1.[CH3:65][N:66]([CH3:95])[C:67]([C@H:69]([N:77]([CH3:94])[C:78](=[O:93])[CH:79]([NH:91][CH3:92])[CH2:80][C:81]1[CH:90]=[CH:89][C:88]2[C:83](=[CH:84][CH:85]=[CH:86][CH:87]=2)[CH:82]=1)[CH2:70][C:71]1[CH:76]=[CH:75][CH:74]=[CH:73][CH:72]=1)=[O:68]>ClCCl>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:17])[NH:18][C:19]([CH3:26])([CH3:27])[CH2:20]/[CH:21]=[CH:22]/[C:23](=[O:24])[N:91]([C@@H:79]([C:78](=[O:93])[N:77]([C@@H:69]([C:67](=[O:68])[N:66]([CH3:65])[CH3:95])[CH2:70][C:71]3[CH:72]=[CH:73][CH:74]=[CH:75][CH:76]=3)[CH3:94])[CH2:80][C:81]3[CH:90]=[CH:89][C:88]4[C:83](=[CH:84][CH:85]=[CH:86][CH:87]=4)[CH:82]=3)[CH3:92])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1

참가 물질

7

반응물 5

HCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22326974HCID 22326974, 화합물HCID 54419464HCID 54419464, 화합물HCID 86587343HCID 86587343, 화합물

생성물 1

HCID 69740563HCID 69740563, 화합물수율 68.1%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (2E)-5-(((9H-flouren-9-yl)methoxy)- carbonylamino)-5-methylhex-2-enoic acid (280 mg, 0.77 mmol) in dichloromethane (5 ml) were added 1-hydroxy-7-azabenzotriazole (126 mg, 0.92 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (207 mg, 1.08 mmol) and the mixture was stirred for 30 min. Then 2R)-N-((1R)-1-dimethylcarbamoyl-2-phenylethyl)-N-methyl-2-methylamino-3-(2-naphthyl)propionamide (386 mg, 0.92 mmol) in dichloromethane (5 ml) and diisoprbpylethylamine (0.17 ml, 1.00 mmol) were added and the mixture was stirred overnight at room temperature. The mixture was washed with water (20 ml), saturated aqueous sodium bicarbonate (20 ml), water (2×20 ml), brine (20 ml), dried over magnesium sulfate and concentrated in vacuo. The crude product was chromatographed on silica (400 g) with ethyl acetate/heptan 1:1 to give 401 mg of ((3E)-4-(N-((1R)-1-(N-((1R)-1-dimethylcarbamoyl-2-phenylethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamoyl)-1,1-dimethylbut-3-enyl)carbamic acid 9H-flouren-9-ylmethyl ester. The obtained product was dissolved in 20% piperidine in dimethylformamide (10 ml) and stirred for 30 min. The mixture was chromatographed on silica (20 g) with dichloromethane/methanol/ammonia 89:10:1 to give 228 mg of (2E)-5-amino-5-methylhex-2-enoic acid N-((1R)-1-(N-((1R)-1-(dimethylcarbamoyl)-2-phenylethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylamide as an oil. The product was redissolved in water (30 ml) and acetic acid (2 ml) was added and the mixture was lyophilized to give 645 mg of the acetate salt of the title compound as an amorphous powder.

후처리

  1. stirringthe mixture was stirred overnight at room temperature
  2. washThe mixture was washed with water (20 ml), saturated aqueous sodium bicarbonate (20 ml), water (2×20 ml), brine (20 ml)
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe crude product was chromatographed on silica (400 g) with ethyl acetate/heptan 1:1

출처 및 근거

ORD 기록
ord-2d80dfcd34ed49b4bdef90580bf064db
출처 데이터셋
uspto-grants-2003_04
특허 번호
US06555570B2

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