Tris(furan-2-yl)phosphane → 7-Benzyl-4-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine

HRID 885054Notes

Reaction equation

HRID 885054 reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14](Cl)=[N:13][CH:12]=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Sn](CCCC)(CCCC)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1)CCC.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>O1CCOCC1.O.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=3)=[N:13][CH:12]=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 521585Tris(furan-2-yl)phosphaneHCID 6077842-(Tributylstannyl)pyridineHCID 219588387-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine

Product 1

HCID 670726517-Benzyl-4-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidineYield 39%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Part C: To a solution of 7-benzyl-4-chloro-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine (4.75 g, 18.3 mmol) in 1,4-dioxane (80 mL) at 25° C. was added sequentially 2-(tributylstannyl)pyridine (98%, 5.95 mL, 18.3 mmol), tri-2-furylphosphine (0.85 g, 3.66 mmol), and palladium (II) acetate (0.205 g, 0.914 mmol). The resulting mixture was heated slowly to reflux over ˜0.25 h and then was stirred at reflux for 5.0 h. After cooling to room temperature the mixture was diluted with water and ethyl acetate, and the mixture filtered. The phases were separated, and the organic phase washed with water and brine, dried over anhyd. sodium sulfate, filtered, and concentrated. Column chromatography (elution: 0-5% 2M ammonia in methanol/chloroform) afforded 7-benzyl-4-(pyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine (2.15 g, 39%) as a red oil; Mass Spec.: m/c: 303.15 (M+H)+ [calc'd: 303.15]; 1H NMR (500 MHz, CDCl3) δ 9.02 (s, 1H), 8.68 (m, 1H), 8.01 (m, 1H), 7.83 (m, 1H), 7.42-7.27 (m, 6H), 3.80 (m, 4H), 3.31 (m, 2H), 2.80 (m, 2H).

Workup

  1. temperatureThe resulting mixture was heated slowly
  2. temperatureto reflux over ˜0.25 h
  3. temperatureat reflux for 5.0 h
  4. filtrationthe mixture filtered
  5. customThe phases were separated
  6. washthe organic phase washed with water and brine
  7. customdried over anhyd
  8. filtrationsodium sulfate, filtered
  9. concentrationconcentrated
  10. washColumn chromatography (elution: 0-5% 2M ammonia in methanol/chloroform)

Sources & evidence

ORD record
ord-1467e1b5591b4010b53fc62bd2dcc48e
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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