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

HRID 530016Notes

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.[CH:12]1(B(O)O)[CH2:14][CH2:13]1.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]([CH:12]2[CH2:14][CH2:13]2)=[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 the title compound from Example 1 Step A (0.250 g, 0.898 mmol), palladium acetate (0.020 g, 0.090 mmol), cyclopropyl boronic acid (0.154 g, 1.80 mmol), cesium carbonate (0.878 g, 2.69 mol), and triphenylphosphine (0.047 g, 0.180 mmol) in tetrahydrofuran (8.98 mL) was heated in a sealed tube at 100° C. for 18 hours. 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 (0-15% ethyl acetate in hexanes) provided the title compound: LCMS m/z 192.93 [M+H]+, 194.89 [M+2+H]+; 1H NMR (500 MHz, CDCl3) δ 8.29 (d, J=7.0 Hz, 1 H), 7.49 (d, J=12.8 Hz, 1 H), 7.21 (dd, J=7.5, 7.5 Hz, 1 H), 6.70 (dd, J=6.3, 6.3 Hz, 1 H), 1.79-1.74 (m, 1 H), 0.98-0.95 (m, 2 H), 0.75-0.73 (m, 2 H).

Workup

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 (0-15% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-1dc68289526642598feed951dcd02a43
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09351973B2

Reaction notes

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