Sodium Bicarbonate → 1-[7-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-butyn-1-ol

HRID 1373792Notes

Reaction equation

[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[C:10]([CH:11]=[O:12])=[C:6]2[CH:5]=[CH:4][CH:3]=1.[C:20]([Mg]Br)#[C:21][CH3:22].C(=O)(O)[O-].[Na+]>O1CCCC1>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[C:10]([CH:11]([OH:12])[C:20]#[C:21][CH3:22])=[C:6]2[CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a cold (−78° C.) suspension of 7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridine-3-carbaldehyde (1.50 g, 5.47 mmol) in tetrahydrofuran (10 mL) was added 1-propynyl magnesium bromide (12.0 mL, 0.5 M in tetrahydrofuran, 6.02 mmol) dropwise. The reaction mixture was stirred at −78° C. for 1 hour, then at 0° C. for 2 hours. The resultant solution was poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with water and brine and the combined organics were dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (4:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) provided 1-[7-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridin-3-yl]-2-butyn-1-ol (1.3 g, 72%) as a white solid. Rf 0.44 (2:1 hexanes:ethyl acetate); 1H NMR (CDCl3) δ 7.99 (d, 1H), 7.78 (m, 2H), 7.14 (m, 3H), 6.95 (d, 1H), 5.70 (m, 1H), 2.21 (d, 1H), 1.85 (d, 3H); MS m/z 315 (M+1).

Workup

waitat 0° C. for 2 hours
extractionextracted with ethyl acetate
washThe organic layer was washed with water and brine
dry with materialthe combined organics were dried over magnesium sulfate
filtrationFiltration and concentration

Sources & evidence

ORD record: ord-8121ae7b67ae48a788c52d117f9cf2ff
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07163940B2

Reaction notes

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