Methanol → 2-(3-Methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carbaldehyde

HRID 59096Notes

Reaction equation

HRID 59096 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:16][C:17]2[N:22]=[C:21]([C:23](OCC)=[O:24])[CH:20]=[C:19]([CH2:28][O:29][CH2:30][C:31]([F:34])([F:33])[F:32])[N:18]=2)[CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[C:13]([CH3:15])[N:12]=[N:11][CH:10]=1.[H-].C([Al+]CC(C)C)C(C)C.CO.O>ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:16][C:17]2[N:22]=[C:21]([CH:23]=[O:24])[CH:20]=[C:19]([CH2:28][O:29][CH2:30][C:31]([F:34])([F:33])[F:32])[N:18]=2)[CH:6]=[CH:7][C:8]=1[C:9]1[CH:14]=[C:13]([CH3:15])[N:12]=[N:11][CH:10]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 21225700Diisobutylaluminumhydride2×HCID 117821334Ethyl 2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)-methyl)pyrimidine-4-carboxylate

Product 1

HCID 1178214562-(3-Methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Ethyl 2-(3-methoxy-4-(6-methylpyridazin-4-yl)phenylamino)-6-((2,2,2-trifluoroethoxy)methyl)-pyrimidine-4-carboxylate (595 mg, 1.25 mmol) was dissolved in dichloromethane (25 mL) under nitrogen atmosphere and cooled at −78° C. Diisobutyl aluminum hydride (1 M in hexane, 4.36 mL, 4.36 mmol) was added over 10 min. After 1 h diisobutyl aluminum hydride (1 M in hexane, 1.4 mL) was added and the mixture was stirred for 2 h. MeOH (3 mL) was added and the mixture was let to rt. Water (5 mL) was added. The slurry was stirred for 20 min and filtrated through a plug of diatomeous earth. The filter plug was washed with 10% MeOH in DCM. The phases were separated and the aqueous phase was extracted with DCM. The combined organic layer was dried over sodium sulfate, filtered and concentrated onto silica. The residue was purified by column chromatography on silica eluting with a gradient of methanol in dichloromethane to give the title compound as a solid, 270 mg (50%).

Workup

  1. customwas let to rt
  2. stirringThe slurry was stirred for 20 min
  3. filtrationfiltrated through a plug of diatomeous earth
  4. washThe filter plug was washed with 10% MeOH in DCM
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with DCM
  7. dry with materialThe combined organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated onto silica
  10. customThe residue was purified by column chromatography on silica eluting with a gradient of methanol in dichloromethane

Sources & evidence

ORD record
ord-f190e3f136af47bd90aa2e821e547f42
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Reaction notes

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