Tricyclohexylphosphine → 8-Cyclopropyl-2-(methylthio)pyrido[3,4-d]pyrimidine

HRID 1480807Notes

Reaction equation

HRID 1480807 reaction equation
Cl[C:2]1[C:7]2[N:8]=[C:9]([S:12][CH3:13])[N:10]=[CH:11][C:6]=2[CH:5]=[CH:4][N:3]=1.[CH:14]1(B(O)O)[CH2:16][CH2:15]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:14]1([C:2]2[C:7]3[N:8]=[C:9]([S:12][CH3:13])[N:10]=[CH:11][C:6]=3[CH:5]=[CH:4][N:3]=2)[CH2:16][CH2:15]1

Participants

7

Reactant 3

HCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 899960258-Chloro-2-(methylthio)pyrido[3,4-d]pyrimidine

Product 1

HCID 899960558-Cyclopropyl-2-(methylthio)pyrido[3,4-d]pyrimidineYield 63.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 22272177Toluene waterSolvent

Conditions

Temperature
95 °C

Procedure

A solution of 8-chloro-2-(methylthio)pyrido[3,4-d]pyrimidine (Preparation 33, 20 mg, 0.094 mmol), cyclopropyl boronic acid (11 mg, 0.128 mmol), PCy3 (3 mg, 10.70 μmol), and Pd(OAc)2 (1 mg, 4.45 μmol) was dissolved in toluene/water 6:1 (1 mL) and heated to 95° C. for 18 hours. The mixture was diluted with EtOAc and quenched with brine. The aqueous layer was extracted with EtOAc three times. The combined organic layers were washed with water and brine, dried and concentrated. The residue was purified by silica gel column chromatography eluting with 0 to 20% EtOAc in cyclohexane to give the title compound (13 mg, 62%).

Workup

  1. customquenched with brine
  2. extractionThe aqueous layer was extracted with EtOAc three times
  3. washThe combined organic layers were washed with water and brine
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting with 0 to 20% EtOAc in cyclohexane

Sources & evidence

ORD record
ord-662bc89102c1460da0de5991eeaf2fea
Source dataset
uspto-grants-2016_08
Patent number
US09409907B2

Reaction notes

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