1-(2,5-Difluoro-4-morpholin-4-ylphenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide → HCID 58072369, compound

HRID 1624710Notes

Reaction equation

HRID 1624710 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[C:5]([F:14])=[CH:4][C:3]=1[N:15]1[CH:20]=[C:19]([O:21][CH3:22])[C:18](=[O:23])[C:17]([C:24](N(OC)C)=[O:25])=[N:16]1.[CH3:30][Mg+].[Br-]>C1COCC1>[C:24]([C:17]1[C:18](=[O:23])[C:19]([O:21][CH3:22])=[CH:20][N:15]([C:3]2[CH:4]=[C:5]([F:14])[C:6]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)=[CH:7][C:2]=2[F:1])[N:16]=1)(=[O:25])[CH3:30]

Participants

4

Reactant 2

HCID 580722751-(2,5-Difluoro-4-morpholin-4-ylphenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideHCID 178418689HCID 178418689, compound

Product 1

HCID 58072369HCID 58072369, compoundYield 77.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1-(2,5-difluoro-4-morpholin-4-ylphenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (0.51 g, 1.2 mmol) in THF (40 mL) was added dropwise to MeMgBr (1.0 M in THF, 5.0 mL, 5.0 mmol) at −78° C. under N2. The mixture was stirred at −78° C. for 2 h. The reaction was quenched with 1 M HCl aqueous solution (5.0 mL) at −78° C. The mixture warmed up to room temperature, diluted with AcOEt, and washed with brine. The organic layer was dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with AcOEt/MeOH (10/0 to 10/1) to give the title compound (340 mg, 75% yield) as a pale yellow solid: NMR (300 MHz, DMSO-d6): δ ppm 2.49 (3H, s), 2.91-3.21 (4H, m), 3.54-3.89 (7H, m), 7.19 (1H, dd, J=12.7, 7.7 Hz), 7.74 (1H, dd, J=12.8, 7.2 Hz), 8.46 (1H, d, J=1.5 Hz). LC-MS (ESI) m/z 366 [M+H]+.

Workup

  1. customThe reaction was quenched with 1 M HCl aqueous solution (5.0 mL) at −78° C
  2. temperatureThe mixture warmed up to room temperature
  3. additiondiluted with AcOEt
  4. washwashed with brine
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with AcOEt/MeOH (10/0 to 10/1)

Sources & evidence

ORD record
ord-f1d210dcc79a45d0a11c6aaff03d9f0c
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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