Diethyl Ether → (S,S)-Azepane-1-carboxylic acid {1-[2-(4-benzyloxy-phenyl)-1-diethylaminomethyl-ethylcarbamoyl]-3-methyl-butyl}-amide

HRID 278890노트

반응식

HRID 278890 반응식
[N:1]1([C:8]([NH:10][C@@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([OH:14])=O)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.[CH2:26]([O:33][C:34]1[CH:39]=[CH:38][C:37]([CH2:40][C@H:41]([NH2:48])[CH2:42][N:43]([CH2:46][CH3:47])[CH2:44][CH3:45])=[CH:36][CH:35]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(OCC)C>CN(C=O)C>[CH2:26]([O:33][C:34]1[CH:35]=[CH:36][C:37]([CH2:40][C@H:41]([NH:48][C:12]([C@@H:11]([NH:10][C:8]([N:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]2)=[O:9])[CH2:15][CH:16]([CH3:18])[CH3:17])=[O:14])[CH2:42][N:43]([CH2:46][CH3:47])[CH2:44][CH3:45])=[CH:38][CH:39]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

참가 물질

6

반응물 4

HCID 3283Diethyl EtherHCID 79724-MethylmorpholineHCID 7530182(2S)-2-(azepane-1-carbonylamino)-4-methylpentanoic acidHCID 59973358(S)-3-(4-benzyloxy-phenyl)-N1,N1-diethyl-propane-1,2-diamine

생성물 1

HCID 9829020(S,S)-Azepane-1-carboxylic acid {1-[2-(4-benzyloxy-phenyl)-1-diethylaminomethyl-ethylcarbamoyl]-3-methyl-butyl}-amide수율 19.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

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온도
25 °C

실험 절차

A solution of 53 mg (0.20 mmol) of (S)-2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid (Example 1, Step B) and 0.079 mL (7.2 mmol) 4-methylmorpholine in 4 mL DMF was stirred at 25° C. for 0.5 hour, and 82 mg (0.21 mmol) 0-benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uronium hexafluorophosphate was added. The resulting solution was cooled in an ice-bath and stirred 30 minutes, after which 64 mg (0.20 mmol) of (S)-3-(4-benzyloxy-phenyl)-N1,N1-diethyl-propane-1,2-diamine in 2 mL DMF was added. The resulting solution was warmed to 25° C. and stirred for 30 minutes. The mixture was then poured into 30 mL diethyl ether, and washed with 25 mL each of 5% HCl solution, brine, saturated aqueous sodium bicarbonate solution, and finally twice with brine. The mixture was dried over anhydrous sodium sulfate and concentrated at reduced pressure to give a clear, colorless oil that was purified by preparative thin-layer chromatography on a 500 μm silica gel plate using 50:50:1 ethyl acetate:hexane:methanol as eluant to give 21.2 mg (19%) of the title compound as a clear, colorless oil.

후처리

  1. temperatureThe resulting solution was cooled in an ice-bath
  2. stirringstirred for 30 minutes
  3. washwashed with 25 mL each of 5% HCl solution, brine, saturated aqueous sodium bicarbonate solution
  4. dry with materialThe mixture was dried over anhydrous sodium sulfate
  5. concentrationconcentrated at reduced pressure
  6. customto give a clear, colorless oil that
  7. customwas purified by preparative thin-layer chromatography on a 500 μm silica gel plate

출처 및 근거

ORD 기록
ord-df1de5fc082b4be487c096f45bc0890c
출처 데이터셋
uspto-grants-2002_03
특허 번호
US06362174B1

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