Potassium Phosphate, Tribasic → 6-Fluoro-2-(5-(2-hydroxypropan-2-yl)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carbonitrile

HRID 705076Notes

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[C:30]=1[C:31]#[N:32].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]([C:30]([C:31]#[N:32])=[C:21]([C:9]3[CH:14]=[N:13][CH:12]=[C:11]([C:15]([OH:18])([CH3:16])[CH3:17])[CH:10]=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 (0.053 g, 0.202 mmol) and the title compound from Example 4 Step A (0.033 g, 0.169 mmol) in tetrahydrofuran (0.84 mL) were added palladium acetate (0.0038 g, 0.017 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (0.014 g, 0.034 mmol), and potassium phosphate tribasic (0.107 g, 0.506 mmol). The resulting mixture was heated at 100° C. for 18 hours, then filtered with the aid of ethyl acetate and concentrated under reduced pressure. Purification by flash chromatography on silica gel (80% acetone in hexanes) provided the title compound: LCMS m/z 296.96 [M+11]+; 1H NMR (500 MHz, CDCl3) δ 9.28 (d, J=1.9 Hz, 1H), 8.87 (d, J=2.0 Hz, 1H), 8.55 (t, J=2.1 Hz, 1H), 8.35 (s, 1H), 7.79 (dd, J=9.8, 4.7 Hz, 1H), 7.45-7.41 (m, 1H), 1.98 (br s, 1H), 1.69 (s, 6H).

Workup

filtrationfiltered with the aid of ethyl acetate
concentrationconcentrated under reduced pressure
customPurification by flash chromatography on silica gel (80% acetone in hexanes)

Sources & evidence

ORD record: ord-9321cca4840b4ba9977dff36f0750369
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09173873B2

Reaction notes

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