Phosphorus oxychloride → 3-(5-Methyl-3-phenyl-isoxazol-4-yl)-imidazo[1,5-a]pyridine

HRID 747858

Reaction equation

HRID 747858 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH:8][C:9]([C:11]1[C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[N:13][O:14][C:15]=1[CH3:16])=O.P(Cl)(Cl)(Cl)=O.C(=O)(O)[O-].[Na+]>ClC(Cl)C.ClCCl>[CH3:16][C:15]1[O:14][N:13]=[C:12]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:11]=1[C:9]1[N:1]2[CH:6]=[CH:5][CH:4]=[CH:3][C:2]2=[CH:7][N:8]=1

Participants

6

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 7008625-methyl-3-phenyl-N-(pyridin-2-ylmethyl)-1,2-oxazole-4-carboxamide

Product 1

HCID 162148953-(5-Methyl-3-phenyl-isoxazol-4-yl)-imidazo[1,5-a]pyridineYield 47.2%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 5-methyl-3-phenyl-isoxazole-4-carboxylic acid (pyridin-2-ylmethyl)-amide (0.293 g, 1 mmol) in dichloroethane (5 mL) was added phosphorus oxychloride (0.47 mL, 5 mmol) via a syringe and the resulting mixture heated under reflux overnight. After cooling to room temperature, the mixture was diluted with dichloromethane. Cold saturated sodium bicarbonate (15 mL) was then added slowly and the mixture was vigorously stirred for 15 min. The organic layer was separated and the aqueous was extracted with dichloromethane. The combined extracts were washed with water, dried over sodium sulphate, and evaporated. Purification by preparative HPLC on reversed phase [0.1% aq. ammonia (25%)] afforded the title compound (0.13 g, 47%) as an orange solid. MS: m/e: 276.1 [M+H]+.

Workup

  1. temperaturethe resulting mixture heated
  2. temperatureunder reflux overnight
  3. customThe organic layer was separated
  4. extractionthe aqueous was extracted with dichloromethane
  5. washThe combined extracts were washed with water
  6. dry with materialdried over sodium sulphate
  7. customevaporated
  8. customPurification by preparative HPLC on reversed phase [0.1% aq. ammonia (25%)]

Sources & evidence

ORD record
ord-4228684736b64a7aa6320801e1172ff2
Source dataset
uspto-grants-2008_07
Patent number
US07399769B2

Linked notes

Loading…