Dimethylformamide → 2-(1-{4-[2-(3,5-Dimethyl-isoxazol-4-yl)-acetylamino]-2-fluoro-phenyl}-piperidin-4-yl)-N,N-diethyl-2-phenyl-acetamide

HRID 1927594노트

반응식

HRID 1927594 반응식
[CH3:1][C:2]1[C:6]([CH2:7][C:8]([OH:10])=O)=[C:5]([CH3:11])[O:4][N:3]=1.CN(C=O)C.C(Cl)(C(Cl)=O)=O.[NH2:23][C:24]1[CH:29]=[CH:28][C:27]([N:30]2[CH2:35][CH2:34][CH:33]([CH:36]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:37]([N:39]([CH2:42][CH3:43])[CH2:40][CH3:41])=[O:38])[CH2:32][CH2:31]2)=[C:26]([F:50])[CH:25]=1>ClCCCl.O>[CH3:1][C:2]1[C:6]([CH2:7][C:8]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([N:30]3[CH2:35][CH2:34][CH:33]([CH:36]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)[C:37]([N:39]([CH2:40][CH3:41])[CH2:42][CH3:43])=[O:38])[CH2:32][CH2:31]3)=[C:26]([F:50])[CH:25]=2)=[O:10])=[C:5]([CH3:11])[O:4][N:3]=1

참가 물질

7

반응물 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 20633382-(Dimethyl-1,2-oxazol-4-yl)acetic acidHCID 693036392-[1-(4-amino-2-fluoro-phenyl)-piperidin-4-yl]-N,N-diethyl-2-phenyl-acetamide

생성물 1

HCID 588707522-(1-{4-[2-(3,5-Dimethyl-isoxazol-4-yl)-acetylamino]-2-fluoro-phenyl}-piperidin-4-yl)-N,N-diethyl-2-phenyl-acetamide수율 56%

시약·촉매·용매 2

HCID 111,2-Dichloroethane용매HCID 962Water용매

실험 절차

A mixture of (3,5-dimethyl-isoxazol-4-yl)-acetic acid (1.0 mmol) and DMF (0.050 mL) in DCE (10 mL) was treated with (COCl)2 (10 mmol), dropwise. The mixture was stirred at rt for 1 h and was concentrated. The residue was diluted with DCE (10 mL) and treated with 2-[1-(4-amino-2-fluoro-phenyl)-piperidin-4-yl]-N,N-diethyl-2-phenyl-acetamide (0.30 mmol) and TEA (2.0 mmol). After 16 h, the mixture was diluted with H2O (10 mL) and extracted. The organic layer was concentrated and the residue was purified by PTLC to provide the title compound (87 mg, 56%). MS (ESI): mass calcd. for C30H37FN4O3, 520.28; m/z found, 521.4 [M+H]+. 1H NMR (CDCl3): 7.40-7.20 (m, 6H), 6.96 (dd, J=8.6, 1.6, 1H), 6.83 (t, J=9.0, 1H), 3.50-3.10 (m, 9H), 2.70-2.60 (m, 1H), 2.52-2.42 (m, 1H), 2.38 (s, 3H), 2.30-2.20 (m, 4H), 2.08-1.98 (m, 1H), 1.50-1.15 (m, 3H), 1.15-1.03 (m, 6H).

후처리

  1. concentrationwas concentrated
  2. additionThe residue was diluted with DCE (10 mL)
  3. waitAfter 16 h
  4. extractionextracted
  5. concentrationThe organic layer was concentrated
  6. customthe residue was purified by PTLC

출처 및 근거

ORD 기록
ord-cce67dbd40fd4a3b98f0b4dbe089e959
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08183239B2

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