1,4-Dioxane → 2-(4-Methylpiperazin-1-yl)-4-(tributylstannyl)pyrimidine

HRID 1969579Notes

Reaction equation

HRID 1969579 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.CS([C:12]1[N:17]=[C:16]([Sn:18]([CH2:27][CH2:28][CH2:29][CH3:30])([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:19][CH2:20][CH2:21][CH3:22])[CH:15]=[CH:14][N:13]=1)(=O)=O.O1CCOCC1>O>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:12]2[N:17]=[C:16]([Sn:18]([CH2:23][CH2:24][CH2:25][CH3:26])([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:19][CH2:20][CH2:21][CH3:22])[CH:15]=[CH:14][N:13]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 531671-MethylpiperazineHCID 142708512-(Methylsulfonyl)-4-(tributylstannyl)pyrimidine

Product 1

HCID 585576732-(4-Methylpiperazin-1-yl)-4-(tributylstannyl)pyrimidineYield 56%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

1-Methylpiperazine (0.160 mL, 1.44 mmol) was added to a solution of 2-(methylsulfonyl)-4-(tributylstannyl)pyrimidine (0.250 g, 0.481 mmol, synthesized as described in Majeed, A. J., et al. Tetrahedron 1989, 45, 993-1006) and 1,4-dioxane (1.0 mL) under nitrogen. After about 2 h, the solution was warmed to about 50° C. After about 30 min, the solution was warmed to about 80° C. After about 30 min, a reflux condenser was attached and the solution was warmed to about 100° C. After about 16 h, the brown solution was allowed to cool to ambient temperature. Water (5 mL) was added. The mixture was extracted with EtOAc (2×5 mL). The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography eluting with a gradient of 2-10% MeOH/DCM to afford 2-(4-methylpiperazin-1-yl)-4-(tributylstannyl)pyrimidine (0.127 g, 56%): 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J=4.6 Hz, 1H), 6.63 (d, J=4.6 Hz, 1H), 3.98-3.82 (m, 4H), 2.63-2.48 (m, 4H), 2.40 (s, 3H), 1.70-1.43 (m, 6H), 1.42-1.20 (m, 6H), 1.18-0.97 (m, 6H), 0.88 (t, J=7.3 Hz, 9H).

Workup

  1. customsynthesized
  2. waitAfter about 30 min
  3. temperaturethe solution was warmed to about 80° C
  4. waitAfter about 30 min
  5. customa reflux condenser was attached
  6. temperaturethe solution was warmed to about 100° C
  7. waitAfter about 16 h
  8. temperatureto cool to ambient temperature
  9. extractionThe mixture was extracted with EtOAc (2×5 mL)
  10. dry with materialThe combined organics were dried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by silica gel chromatography
  14. washeluting with a gradient of 2-10% MeOH/DCM

Sources & evidence

ORD record
ord-de54e826edbe47479fa2bcedc24429a8
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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