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

HRID 657775Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:31][CH2:30][C:13]3[N:14]=[CH:15][N:16]=[C:17]([NH:18][CH2:19][C:20]4[CH:21]=[N:22][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:24][CH:25]=4)[C:12]=3[CH2:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8].[CH3:32]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>[CH3:32][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH2:31][CH2:30][C:13]3[N:14]=[CH:15][N:16]=[C:17]([NH:18][CH2:19][C:20]4[CH:21]=[N:22][C:23]([C:26]([F:28])([F:29])[F:27])=[CH:24][CH:25]=4)[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 5-bromo-2-(4-((6-(trifluoromethyl)pyridin-3-yl)methylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile (120 mg, 0.24 mmol), methylboronic acid (19 mg, 0.32 mmol), potassium phosphate (182 mg, 0.86 mmol), tricyclohexylphosphine (6.9 mg, 0.024 mmol), toluene (5 mL), and water (0.5 mL) under argon was added palladium acetate (2.8 mg, 0.012 mmol). The mixture was heated at 100° C. for 20 h and then cooled to rt. The mixture was filtered and concentrated. The residue was purified by semi-preparative HPLC to yield an off-white solid (75 mg, 71%).

Workup

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

Sources & evidence

ORD record: ord-4d254b71f8f34c74a24df5d4dce47a4d
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08076345B2

Reaction notes

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