Potassium Phosphate, Tribasic → 2-(5-(6-Fluoroimidazo[1,2-a]pyridin-2-yl)pyridin-3-yl)propan-2-ol

HRID 705070Notes

Reaction equation

CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([C:15]([OH:18])([CH3:17])[CH3:16])[CH:12]=[N:13][CH:14]=2)O1.Cl[C:21]1[N:22]=[C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][N:24]2[CH:30]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:29][C:26]1[CH:27]=[CH:28][C:23]2[N:24]([CH:30]=[C:21]([C:9]3[CH:10]=[C:11]([C:15]([OH:18])([CH3:16])[CH3:17])[CH:12]=[N:13][CH:14]=3)[N:22]=2)[CH:25]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of the title compound from Example 2 Step D (0.1855 g, 0.704 mmol) and the title compound from Example 2 Step B (0.10 g, 0.586 mmol) in tetrahydrofuran (5.86 mL) were added palladium acetate (0.013 g, 0.059 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.048 g, 0.117 mmol), and potassium phosphate tribasic (0.373 g, 1.759 mmol). The resulting mixture was heated at 100° C. for 18 hours. The mixture was then cooled to room temperature, filtered with the aid of ethyl acetate, and concentrated under reduced pressure. Purification by flash chromatography on silica gel (30-50% acetone in dichloromethane) provided the title compound: LCMS m/z 273.99 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.99 (d, J=1.6 Hz, 1H), 8.72 (d, J=2.2 Hz, 1H), 8.39 (t, J=2.0 Hz, 1H), 8.10 (t, J=2.6 Hz, 1H), 7.96 (s, 1H), 7.63 (dd, J=9.9, 4.8 Hz, 1H), 7.17-7.13 (m, 1H), 2.00 (br s, 1H), 1.68 (s, 6H).

Workup

temperatureThe mixture was then cooled to room temperature
filtrationfiltered with the aid of ethyl acetate
concentrationconcentrated under reduced pressure
customPurification by flash chromatography on silica gel (30-50% acetone in dichloromethane)

Sources & evidence

ORD record: ord-9a82523955cc4824a5c773e7828d0fc3
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09173873B2

Reaction notes

Loading…