3-Oxo-3-(pyridin-4-yl)propanenitrile → 2-Methyl-3-(2-methyl-3-(trifluoromethyl)benzyl)-5-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-amine

HRID 510371Notes

Reaction equation

[CH3:1][C:2]1[C:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[C:9]=2[CH3:18])=[C:5]([NH2:19])[NH:4][N:3]=1.O=[C:21]([C:25]1[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=1)[CH2:22][C:23]#[N:24]>C(O)(=O)C>[CH3:1][C:2]1[C:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:17])[F:16])[C:9]=2[CH3:18])=[C:5]2[N:19]=[C:21]([C:25]3[CH:30]=[CH:29][N:28]=[CH:27][CH:26]=3)[CH:22]=[C:23]([NH2:24])[N:4]2[N:3]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a suspension of 3-methyl-4-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-1H-pyrazol-5-amine (100 mg, 0.37 mmol) in acetic acid (2 mL) was added 3-oxo-3-(4-pyridinyl)propanenitrile (54.3 mg, 0.37 mmol). The reaction mixture was irradiated (microwave) and stirred at 140° C. for 40 minutes. Reaction mixture was cooled down, diluted with acetic acid (2 mL) and stood still overnight. Precipitate was collected by filtration. The crude product was purified with column chromatography to provide titled product. (23 mg, 16%); LC/MS: MS (ES+) m/e 398 (MH+); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.57 (s, 3H) 1.72 (s, 3H) 3.44 (s, 2H) 6.01 (s, 1H) 6.45 (d, J=7.58 Hz, 1H) 6.50-6.55 (m, 1H) 6.73 (d, J=7.58 Hz, 1H) 7.72-7.80 (m, 2H) 8.03-8.10 (m, 2H).

Workup

customThe reaction mixture was irradiated (microwave)
customReaction mixture
temperaturewas cooled down
waitstood still overnight
filtrationPrecipitate was collected by filtration
customThe crude product was purified with column chromatography

Sources & evidence

ORD record: ord-dae56a713dda4de78b6c479743a381e4
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096605B2

Reaction notes

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