4,6-Dichloro-5-pyrimidinecarbaldehyde → HCID 86677188, compound

HRID 2405895Notes

Reaction equation

HRID 2405895 reaction equation
Br[C:2]1[C:7]([F:8])=[C:6]([Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[C:5]([F:16])=[C:4]([F:17])[N:3]=1.C([Li])CCC.[Cl:23][C:24]1[C:29]([CH:30]=[O:31])=[C:28]([Cl:32])[N:27]=[CH:26][N:25]=1>C1COCC1>[Si:9]([C:6]1[C:5]([F:16])=[C:4]([F:17])[N:3]=[C:2]([CH:30]([C:29]2[C:24]([Cl:23])=[N:25][CH:26]=[N:27][C:28]=2[Cl:32])[OH:31])[C:7]=1[F:8])([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 8196914,6-Dichloro-5-pyrimidinecarbaldehydeHCID 86677189HCID 86677189, compoundHCID 178418339Butyllithium

Product 1

HCID 86677188HCID 86677188, compoundYield 37.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of (2-bromo-3,5,6-trifluoro-4-pyridyl)-tert-butyl-dimethyl-silane (2.5 g, 7.66 mmol) in THF (15 mL) cooled at −78° C. was added butyllithium (2.5M in hexanes) (3.22 mL of 2.5 M, 8.05 mmol) at a rate which maintained the temperature below −70° C. On complete addition, the reaction mixture was stirred at −78° C. for 40 minutes and then a solution of 4,6-dichloropyrimidine-5-carbaldehyde (1.43 g, 8.05 mmol) in THF (25 mL) was added at a rate which maintained the temperature below −70° C. The reaction mixture was stirred at −78° C. for 1.5 hours. After this time, the reaction mixture was quenched with water and extracted with EtOAc (3×). The organics were combined, washed with water, brine, dried (MgSO4), filtered and concentrated in vacuo. The crude mixture was purified by column chromatography (ISCO Companion™, 80 g column, eluting with 0-5% EtOAc/petroleum ether) to give the sub title compound as a cream solid (1.21 g, 37.2% Yield). H1 NMR (400 MHz, DMSO) δ 8.91 (1H, s), 6.69 (1H, s), 6.48 (1H, s), 0.88 (9H, s) and 0.39 (6H, s).

Workup

  1. temperaturemaintained the temperature below −70° C
  2. additionOn complete addition
  3. temperaturemaintained the temperature below −70° C
  4. stirringThe reaction mixture was stirred at −78° C. for 1.5 hours
  5. customAfter this time, the reaction mixture was quenched with water
  6. extractionextracted with EtOAc (3×)
  7. washwashed with water, brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe crude mixture was purified by column chromatography (ISCO Companion™, 80 g column, eluting with 0-5% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-084b834a215e424cb24755eea234849d
Source dataset
uspto-grants-2014_08
Patent number
US08809335B2

Reaction notes

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