N,N-Diethylaniline → HCID 71527716, compound

HRID 510379Notes

Reaction equation

HRID 510379 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:12][C:13]1[CH:14]=[N:15][N:16]2[C:21](=O)[CH:20]=[C:19]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[NH:18][C:17]=12.C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)([Cl:42])=O>>[Cl:42][C:21]1[N:16]2[N:15]=[CH:14][C:13]([CH2:12][C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([F:11])([F:10])[F:9])[C:2]=3[CH3:1])=[C:17]2[N:18]=[C:19]([N:23]2[CH2:24][CH2:25][O:26][CH2:27][CH2:28]2)[CH:20]=1

Participants

4

Reactant 3

HCID 7061N,N-DiethylanilineHCID 24813Phosphorus oxychlorideHCID 178422945HCID 178422945, compound

Product 1

HCID 71527716HCID 71527716, compound

Conditions

Temperature
80 °C

Procedure

To a suspension of 3-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-5-(4-morpholinyl)pyrazolo[1,5-a]pyrimidin-7(4H)-one (0.52 g, 1.32 mmol) and N,N-diethylaniline (0.43 g, 2.92 mmol) under nitrogen was added neat phosphoric trichloride (1.12, 6.63 mmol) dropwise during 15 minutes. The reaction mixture was stirred at 80° C. for 3 hours. Reaction mixture was concentrated under reduce pressure. The residue was dissolved with DCM (50 mL) and water (15 mL). The pH of aqueous layer was adjusted to 8˜9. Two layers were separated. Aqueous layer was then extracted with DCM (30 mL×3). The crude material was then purified with silica gel column chromatography (CH3OH/DCM 0-10%) to provide the titled product. (450 mg, 83%); LC/MS: MS (ES+) m/e 378 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 3.43 (br. s., 1H) 3.45 (d, J=5.05 Hz, 3H) 3.63-3.71 (m, 4H) 4.00 (s, 2H) 5.55 (s, 1H) 7.16 (s, 2H) 7.22-7.30 (m, 1H) 7.30-7.40 (m, 1H) 7.46 (dd, J=7.83, 1.77 Hz, 1H) 7.72 (s, 1H).

Workup

  1. customReaction mixture
  2. concentrationwas concentrated
  3. dissolutionThe residue was dissolved with DCM (50 mL) and water (15 mL)
  4. customTwo layers were separated
  5. extractionAqueous layer was then extracted with DCM (30 mL×3)
  6. customThe crude material was then purified with silica gel column chromatography (CH3OH/DCM 0-10%)

Sources & evidence

ORD record
ord-a698c042bf304812b3ea884c11b16b71
Source dataset
uspto-grants-2015_08
Patent number
US09096605B2

Reaction notes

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