Potassium Phosphate, Tribasic → 2-(5-(Pyrazolo[1,5-a]pyridin-2-yl)pyridin-3-yl)propan-2-ol

HRID 530019Notes

Reaction equation

Cl[C:2]1[CH:10]=[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.CC1(C)C(C)(C)OB([C:19]2[CH:20]=[C:21]([C:25]([OH:28])([CH3:27])[CH3:26])[CH:22]=[N:23][CH:24]=2)O1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCCC1.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:3]1[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]2=[CH:10][C:2]=1[C:19]1[CH:20]=[C:21]([C:25]([OH:28])([CH3:27])[CH3:26])[CH:22]=[N:23][CH:24]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 2-chloro-pyrazolo[1,5-a]pyridine (0.200 g, 1.31 mmol) and the title compound from Example 1 Step D (0.414 g, 1.573 mmol) in tetrahydrofuran (6.55 mL) were added palladium acetate (0.029 g, 0.131 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.108 g, 0.262 mmol), and potassium phosphate tribasic (0.835 g, 3.93 mmol). The resulting mixture was heated at 100° C. for 18 hours, then diluted with ethyl acetate, filtered, and concentrated under reduced pressure. Purification by flash chromatography on silica gel (0-15% ethyl acetate in hexanes) provided the title compound: LCMS m/z 254.02 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.05 (s, 1 H), 8.74 (s, 1 H), 8.49 (d, J=6.9 Hz, 2 H), 8.40 (s, 1 H), 7.55 (d, J=6.9 Hz, 2 H), 7.15 (dd, J=7.6, 7.9 Hz, 1 H), 6.86 (s, 1 H), 6.79 (dd, J=7.1, 6.6 Hz, 1 H), 1.68 (s, 6 H).

Workup

filtrationfiltered
concentrationconcentrated under reduced pressure
customPurification by flash chromatography on silica gel (0-15% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-8f26757a480f4f03a14558683ff76bca
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09351973B2

Reaction notes

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