Acetyl chloride → N-(4-(5-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(3-chloro-4-cyano-2-methylphenylamino)propyl)-1,3,4-oxadiazol-2-yl)phenyl)acetamide

HRID 563336노트

반응식

HRID 563336 반응식
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([C@H:13]([NH:24][C:25]3[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([Cl:33])[C:26]=3[CH3:34])[C@H:14]([O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH3:15])=[N:10][N:9]=2)=[CH:4][CH:3]=1.[C:35](Cl)(=[O:37])[CH3:36]>C(Cl)Cl.N1C=CC=CC=1>[Si:17]([O:16][C@H:14]([CH3:15])[C@H:13]([C:11]1[O:12][C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:35](=[O:37])[CH3:36])=[CH:7][CH:6]=2)=[N:9][N:10]=1)[NH:24][C:25]1[CH:32]=[CH:31][C:28]([C:29]#[N:30])=[C:27]([Cl:33])[C:26]=1[CH3:34])([C:20]([CH3:22])([CH3:23])[CH3:21])([CH3:19])[CH3:18]

참가 물질

5

반응물 2

HCID 6367Acetyl chlorideHCID 591930604-((1R,2R)-1-(5-(4-Aminophenyl)-1,3,4-oxadiazol-2-yl)-2-(tert-butyldimethylsilyloxy)propylamino)-2-chloro-3-methylbenzonitrile2회

생성물 1

HCID 59193053N-(4-(5-((1R,2R)-2-(tert-Butyldimethylsilyloxy)-1-(3-chloro-4-cyano-2-methylphenylamino)propyl)-1,3,4-oxadiazol-2-yl)phenyl)acetamide수율 100%

시약·촉매·용매 2

HCID 1049Pyridine용매HCID 6344Dichloromethane용매

실험 절차

To a solution of 4-((1R,2R)-1-(5-(4-aminophenyl)-1,3,4-oxadiazol-2-yl)-2-(tert-butyldimethylsilyloxy)propylamino)-2-chloro-3-methylbenzonitrile (intermediate 69d) (311 mg, 0.62 mmol) in CH2Cl2 (10 mL) and pyridine (1.5 mL) was added acetylchloride (62 μL, 0.87 mmol) at room temperature. The resultant solution stirred for 89 hours and quenched with 2N aq. HCl (15 mL). The mixture was further partitioned between H2O (40 mL) and CH2Cl2 (40 mL). The aqueous layer was extracted with CH2Cl2 (35 mL). The combined organic extracts were washed with sat. aq. NaHCO3 (2×45 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provide a colourless oil (335 mg, 100%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 9.49 (s 1H), 7.93 (dm, J=8.8 Hz, 2H), 7.83 (dm, J=8.8 Hz, 2H), 7.50 (d, J=8.6 Hz, 1H), 6.94 (d, J=8.8 Hz, 1H), 5.74 (d, J=9.0 Hz, 1H), 5.03 (dd, J=6.4, 9.0 Hz, 1H), 4.65 (pentet, J=6.4 Hz, 1H), 2.34 (s, 3H), 2.12 (s, 3H), 1.44 (d, J=6.1 Hz, 3H), 0.81 (s, 9H), 0.09 (s, 3H), −0.02 (s, 3H).

후처리

  1. customquenched with 2N aq. HCl (15 mL)
  2. customThe mixture was further partitioned between H2O (40 mL) and CH2Cl2 (40 mL)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (35 mL)
  4. washThe combined organic extracts were washed with sat. aq. NaHCO3 (2×45 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-091fd034da564e9fb06eb3b12fc5542d
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08067448B2

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