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 1927594ノート

反応式

HRID 1927594 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 962Water溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-cce67dbd40fd4a3b98f0b4dbe089e959
出典データセット
uspto-grants-2012_05
特許番号
US08183239B2

反応ノート

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