Diisopropylamine → (+/-)-1,2,2-Tripyridin-3-yl-1-pyrimidin-4-ylethanol

HRID 2099581Notes

Reaction equation

HRID 2099581 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH2:19][C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[CH:14]=1.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([C:34]2[CH:39]=[CH:38][N:37]=[CH:36][N:35]=2)=[O:33])[CH:27]=1>C1COCC1>[N:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([C:34]2[CH:39]=[CH:38][N:37]=[CH:36][N:35]=2)([OH:33])[CH:19]([C:20]2[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=2)[C:15]2[CH:14]=[N:13][CH:18]=[CH:17][CH:16]=2)[CH:27]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 105355204-(Pyridine-3-carbonyl)pyrimidineHCID 147626403,3'-MethylenedipyridineHCID 178418339Butyllithium

Product 1

HCID 11559467(+/-)-1,2,2-Tripyridin-3-yl-1-pyrimidin-4-ylethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

In a flame dried flask under N2, diisopropylamine (0.079 mL, 0.56 mmol) was dissolved in THF (1 mL). The solution was cooled to 0° C. n-Butyl-lithium (2.5 M solution in hexanes, 0.215 mL, 0.54 mmol) was slowly added and the reaction was stirred at 0° C. for 15 min. A solution of 3-(pyridin-3-ylmethyl)pyridine (0.087 g, 0.51 mmol) in THF (1mL) was slowly added drop-wise. The reaction became dark red. After 10 min. a solution of pyridin-3-yl(pyrimidin-4-yl)methanone (0.099 g, 0.54 mmol, J. Heterocyclic Chem., 34, 17 (1997)) in THF (1 mL) was slowly added drop-wise. The reaction was stirred at 0° C. for 3 hr then removed from the ice bath. Sat. aq. NH4Cl (20 mL) was added and the reaction was stirred vigorously. The product was extracted with EtOAc (4×50 mL). The combined organics were dried over Na2SO4, filtered and concentrated to afford an oil which was purified by reverse phase HPLC (5-95% CH3CN/H2O+0.05% NH4OH). The fractions were combined and concentrated in vacuo to afford the title compound as a white solid. 1H NMR (CDCl3) δ 9.01 (d, 1H, J=1.22 Hz), 8.85 (d, 1H, J=1.95 Hz), 8.70 (d, 1H, J=5.37 Hz), 8.58 (d, 1H, J=2.19 Hz), 8.42 (dd, 1H, J=1.46 Hz), 8.38-8.33 (m, 3H), 7.94-7.87 (m, 2H), 7.70-7.67 (m, 1H), 7.07 (dd, 1H, J=1.22 Hz), 7.19-7.14 (m, 1H), 7.13-7.08 (m, 2H), 5.98 (s, 1H), 5.12 (s, 1H). HRMS m/z (M+H) Calculated: 356.1506, found: 356.1519.

Workup

  1. customIn a flame dried flask under N2
  2. additionwas slowly added
  3. stirringThe reaction was stirred at 0° C. for 3 hr
  4. customthen removed from the ice bath
  5. additionSat. aq. NH4Cl (20 mL) was added
  6. stirringthe reaction was stirred vigorously
  7. extractionThe product was extracted with EtOAc (4×50 mL)
  8. dry with materialThe combined organics were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford an oil which
  12. customwas purified by reverse phase HPLC (5-95% CH3CN/H2O+0.05% NH4OH)
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-41b7afb612214c80a4ac454d8ce0e3d9
Source dataset
uspto-grants-2009_08
Patent number
US07569589B2

Reaction notes

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