Potassium Phosphate, Tribasic → 5-Cyclopropyl-2-{4-[(6-trifluoromethyl-pyridin-3-ylmethyl)-amino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-benzonitrile

HRID 657776Notes

Reaction equation

HRID 657776 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].[CH:32]1(B(O)O)[CH2:34][CH2:33]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O.O.C1(C)C=CC=CC=1>[CH:32]1([C:2]2[CH:3]=[CH:4][C:5]([N:10]3[CH2:31][CH2:30][C:13]4[N:14]=[CH:15][N:16]=[C:17]([NH:18][CH2:19][C:20]5[CH:21]=[N:22][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:24][CH:25]=5)[C:12]=4[CH2:11]3)=[C:6]([CH:9]=2)[C:7]#[N:8])[CH2:34][CH2:33]1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 250618715-bromo-2-(4-((6-(trifluoromethyl)pyridin-3-yl)methylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)benzonitrile

Product 1

HCID 250618725-Cyclopropyl-2-{4-[(6-trifluoromethyl-pyridin-3-ylmethyl)-amino]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl}-benzonitrileYield 59.8%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

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 (13 mg, 0.026 mmol), cyclopropylboronic acid (3.0 mg, 0.034 mmol), potassium phosphate (20 mg, 0.093 mmol), tricyclohexylphosphine (2.5 mg, 0.0090 mmol), toluene (2.0 mL), and water (0.04 mL) under argon was added palladium acetate (1.0 mg, 0.0044 mmol). The mixture was heated at 100° C. for 3 h and then cooled to rt. Water (10 mL) and EtOAc (100 mL) were added. The organic layer was separated and washed with brine, dried (Na2SO4), and concentrated. The residue was purified by semi-preparative HPLC to yield a white solid (7 mg, 58%).

Workup

  1. temperaturecooled to rt
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue was purified by semi-preparative HPLC

Sources & evidence

ORD record
ord-180a8ec53776440bb3ca0faabce77c7f
Source dataset
uspto-grants-2011_12
Patent number
US08076345B2

Reaction notes

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