N,N-Diethylaniline → 7-chloro-2-methyl-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-5-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidine

HRID 510369Notes

Reaction equation

HRID 510369 reaction equation
C(N(CC)C1C=CC=CC=1)C.[CH3:12][C:13]1[C:28]([CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[C:31]=2[CH3:40])=[C:16]2[NH:17][C:18]([CH:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:19][C:20](=O)[N:15]2[N:14]=1.P(Cl)(Cl)([Cl:43])=O>>[Cl:43][C:20]1[N:15]2[N:14]=[C:13]([CH3:12])[C:28]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[C:31]=3[CH3:40])=[C:16]2[N:17]=[C:18]([CH:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH:19]=1

Participants

4

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178433774HCID 178433774, compound

Product 1

HCID 867248677-chloro-2-methyl-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-5-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidine

Conditions

Temperature
0 °C

Procedure

To a suspension of N,N-diethylaniline (0.83 g, 5.54 mmol) and 2-methyl-3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-5-(tetrahydro-2H-pyran-4-yl)pyrazolo[1,5-a]pyrimidin-7(4H)-one (1.02 g, 2.52 mmol) stirred under nitrogen at 0° C. was added neat phosphoric trichloride (1.93 g, 12.6 mmol) dropwise during 5 minutes. The reaction mixture was stirred at 80° C. for 2 hr. Reaction mixture was concentrated. The residue was dissolved with DCM (50 mL) and icy water (15 mL). The pH of aqueous layer was adjusted by 10 N NaOH solution to 5. Two layers were separated. Organic layer was washed with brine (15 mL) again. Organic layer was dried, concentrated to dryness. Product was purified on a silica gel column (ethyl acetate/hexane gradient solvents). The product was obtained and used in subsequent steps. (463 mg, 43%); LC/MS: MS (ES+) m/e 424 (MH+).

Workup

  1. stirringThe reaction mixture was stirred at 80° C. for 2 hr
  2. customReaction mixture
  3. concentrationwas concentrated
  4. dissolutionThe residue was dissolved with DCM (50 mL) and icy water (15 mL)
  5. customTwo layers were separated
  6. washOrganic layer was washed with brine (15 mL) again
  7. customOrganic layer was dried
  8. concentrationconcentrated to dryness
  9. customProduct was purified on a silica gel column (ethyl acetate/hexane gradient solvents)
  10. customThe product was obtained

Sources & evidence

ORD record
ord-f071c6c05927475eabdef6f065714751
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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