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

HRID 861142Notes

Reaction equation

[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=3)[C:10]([CH:11]=[O:12])=[C:6]2[CH:5]=[CH:4][CH:3]=1.[C:20]([Mg]Br)#[CH:21].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][CH:16]=[C:15]([CH3:19])[CH:14]=3)[C:10]([CH:11]([OH:12])[C:20]#[CH:21])=[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-(3-methylphenyl)pyrazolo[1,5-a]pyridine-3-carbaldehyde (10.38 g, 36.2 mmol) in tetrahydrofuran (80 mL) was added ethynylmagnesium bromide (87 mL, 0.5 M in tetrahydrofuran, 43.4 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 7:3 hexanes:ethyl acetate) provided 1-[7-chloro-2-(3-methylphenyl)pyrazolo[1,5-a]pyridin-3-yl]-2-propyn-1-ol (11.3 g, 77%) as a yellow foam. 1H NMR (CDCl3) δ 8.03 (d, 1H), 7.60 (s, 1H), 7.54 (d, 1H), 7.37 (t, 1H), 7.26 (d, 1H), 7.17 (dd, 1H), 6.98 (d, 1H), 2.67 (s, 1H), 2.43 (s, 3H), 2.38 (s, 1H); MS m/z297 (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-fcc6329a489e42b48bae9926850c1ffe
Source dataset: uspto-grants-2006_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07153855B2

Reaction notes

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