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 2388538ノート

反応式

HRID 2388538 の反応式
[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]

参加物

5

反応物 2

HCID 6367Acetyl chlorideHCID 591930604-((1R,2R)-1-(5-(4-Aminophenyl)-1,3,4-oxadiazol-2-yl)-2-(tert-butyldimethylsilyloxy)propylamino)-2-chloro-3-methylbenzonitrile2 回

生成物 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)acetamide収率 100%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-e5a99a1cfdc746f6b8e2e82ebf436f9a
出典データセット
uspto-grants-2012_09
特許番号
US08268872B2

反応ノート

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