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

HRID 530032Notes

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 2-chloro-3-iodopyrazolo-[1,5-a]pyridine (27-3; 0.7 g, 2.52 mmol), cyclopropyl boronic acid (0.43 g, 5.036 mmol), and cesium carbonate (2.46 g, 7.56 mmol), in tetrahydrofuran (15.0 mL) was degassed for 10 min. Then triphenylphosphine (0.132 g, 0.504 mmol) and palladium acetate (0.056 g, 0.252 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-cyclopropylpyrazolo[1,5-a]pyridine. 1H NMR (400 MHz, CDCl3) δ 8.29-8.27 (d, J=7.2 Hz, 1 H), 7.50-7.48 (d, J=8.8 Hz, 1 H), 7.11-7.07 (t, J=7.8 Hz, 1 H), 6.72-6.69 (m, 1 H), 1.80-1.73 (m, 1 H), 0.98-0.95 (m, 2 H), 0.75-0.73 (m, 2 H). MS (M+1): 139.1.

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 (0-5% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-d627c17449db46f8acb10a2d0803dcae
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09351973B2

Reaction notes

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