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 1927594Notes

Reaction equation

HRID 1927594 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-cce67dbd40fd4a3b98f0b4dbe089e959
Source dataset
uspto-grants-2012_05
Patent number
US08183239B2

Reaction notes

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