Cesium carbonate → 2-Chloro-3-methylpyrazolo[1,5-A]pyridine

HRID 530036Notes

Reaction equation

[Cl:1][C:2]1[C:10](I)=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:12]B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[C:10]([CH3:12])=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-chloro-3-iodopyrazolo[1,5-a]pyridine (27-3; 0.8 g, 2.87 mmol), methyl boronic acid (0.345 g, 5.7 mmol), and cesium carbonate (2.8 g, 8.61 mmol) in tetrahydrofuran (15 mL) was degassed for 10 min. Then triphenylphosphine (0.15 g, 0.574 mmol) and palladium acetate (0.064 g, 0.287 mmol) were added and heated in a sealed tube at 100° C. for 18 h. The reaction mixture was then cooled to room temperature, filtered and concentrated under reduced pressure. Purification of the resulting residue by flash chromatography on silica gel (0-5% ethyl acetate in hexanes) provided 2-chloro-3-methylpyrazolo[1,5-a]pyridine. 1H NMR (400 MHz, DMSO-d6) δ 8.55-8.53 (d, J=8 Hz, 1 H), 7.61-7.59 (d, J=8 Hz, 1 H), 7.25-7.21 (t, J=8 Hz, 1 H), 6.89-6.86 (t, J=8 Hz, 1 H), 2.19 (s, 3 H). MS (M+1): 167.1.

Workup

customwas degassed for 10 min
temperatureThe reaction mixture was then cooled to room temperature
filtrationfiltered
concentrationconcentrated under reduced pressure
customPurification of the resulting residue by flash chromatography on silica gel (0-5% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-d1f0c12ca57a4147a77e25b6b93d2768
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09351973B2

Reaction notes

Loading…