Diisopropylethylamine → 4-(3-(5-bromopyridin-2-yloxy)benzylidene)-N-(3,4-dimethylisoxazol-5-yl)piperidine-1-carboxamide

HRID 1666375Notes

Reaction equation

HRID 1666375 reaction equation
FC(F)(F)C(O)=O.[Br:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]=[C:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[CH:17]=2)=[N:13][CH:14]=1.[CH3:29][C:30]1[C:34]([CH3:35])=[C:33]([NH:36][C:37](=O)[O:38]C2C=CC=CC=2)[O:32][N:31]=1.CC1C(C)=C(N)ON=1.C(N(C(C)C)CC)(C)C>C(#N)C>[Br:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][C:16]2[CH:17]=[C:18]([CH:19]=[CH:20][CH:21]=2)[CH:22]=[C:23]2[CH2:24][CH2:25][N:26]([C:37]([NH:36][C:33]3[O:32][N:31]=[C:30]([CH3:29])[C:34]=3[CH3:35])=[O:38])[CH2:27][CH2:28]2)=[N:13][CH:14]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 883175-Amino-3,4-dimethylisoxazoleHCID 53485970Phenyl (3,4-dimethylisoxazol-5-yl)carbamateHCID 668761435-Bromo-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate

Product 1

HCID 249640574-(3-(5-bromopyridin-2-yloxy)benzylidene)-N-(3,4-dimethylisoxazol-5-yl)piperidine-1-carboxamideYield 96%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

5-Bromo-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate (0.584 mmol, from Step 5), in acetonitrile (1.75 mL) was treated with phenyl 3,4-dimethylisoxazol-5-ylcarbamate (100 mg, 0.467 mmol, prepared according to the procedure described in Synthesis, 1997, 1189-1194 from 3,4-dimethylisoxazol-5-amine) and diisopropylethylamine (0.305 mL, 1.75 mmol) and stirred at room temperature. After 2 h, the reaction was concentrated and the residue was purified by flash chromatography on silica gel (0-6% ethanol (containing 11% aq NH4OH):dichloromethane) to afford a clear oil which was evaporated from isopropyl ether/dichloromethane and evaporated again from diethyl ether/dichloromethane to give the title compound (0.200 g, 96% yield) as a white foam. MS (APCI) M+1=483.1; 1H NMR (400 MHz, CDCl3) δ ppm 1.89 (s, 3H) 2.20 (s, 3H) 2.43-2.49 (m, 2H) 2.56-2.62 (m, 2H) 3.45-3.52 (m, 2H) 3.56-3.62 (m, 2H) 6.41 (br. s, 1H) 6.61 (br. s, 1H) 6.86 (dd, J=8.68, 0.49 Hz, 1H) 6.95-7.02 (m, 2H) 7.04-7.09 (m, 1H) 7.37 (t, J=7.90 Hz, 1H) 7.79 (dd, J=8.58, 2.53 Hz, 1H) 8.22-8.24 (m, 1H).

Workup

  1. customprepared
  2. concentrationthe reaction was concentrated
  3. customthe residue was purified by flash chromatography on silica gel (0-6% ethanol (containing 11% aq NH4OH):dichloromethane)
  4. customto afford a clear oil which
  5. customwas evaporated from isopropyl ether/dichloromethane
  6. customevaporated again from diethyl ether/dichloromethane

Sources & evidence

ORD record
ord-fd3e56792a18456cb5201d03b4a97f98
Source dataset
uspto-grants-2011_10
Patent number
US08044052B2

Reaction notes

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