Potassium Phosphate, Tribasic → (R)-5-Methyl-2-(4-(1-(6-(trifluoromethyl)pyridin-3-yl)ethylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile

HRID 657780Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:32][CH2:31][C:13]3[N:14]=[CH:15][N:16]=[C:17]([NH:18][C@@H:19]([C:21]4[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=4)[CH3:20])[C:12]=3[CH2:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH3:33]B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH3:33][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:32][CH2:31][C:13]3[N:14]=[CH:15][N:16]=[C:17]([NH:18][C@@H:19]([C:21]4[CH:22]=[N:23][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:25][CH:26]=4)[CH3:20])[C:12]=3[CH2:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8]

Participants

Conditions

Temperature: 100 °C

Procedure

To a mixture of (R)-5-bromo-2-(4-(1-(6-(trifluoromethyl)pyridin-3-yl)ethylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile (240 mg, 0.48 mmol), methylboronic acid (37.0 mg, 0.619 mmol), potassium phosphate (354 mg, 1.67 mmol), tricyclohexylphosphine (25 mg, 0.089 mmol), toluene (10 mL), and water (0.6 mL) under argon was added palladium acetate (10 mg, 0.04 mmol). The mixture was heated at 100° C. for 3 h and then cooled to rt. The mixture was filtered and concentrated. The residue was purified by semi-preparative HPLC to yield a light yellow solid (145 mg, 69%).

Workup

temperaturecooled to rt
filtrationThe mixture was filtered
concentrationconcentrated
customThe residue was purified by semi-preparative HPLC

Sources & evidence

ORD record: ord-de2725a64bf14205991e0e86022ae8a0
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08076345B2

Reaction notes

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