Water → 1-[4-(3,4-Difluoro-1H-pyrrol-1-yl)-2-fluorophenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 2089997Notes

Reaction equation

HRID 2089997 reaction equation
CC([O-])(C)C.[K+].[F:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:18][C:17](F)([F:19])[C:16](F)([F:21])[CH2:15]2)[CH:11]=[CH:10][C:9]=1[N:23]1[CH:28]=[C:27]([O:29][CH3:30])[C:26](=[O:31])[C:25]([C:32]2[N:36]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:35]=[CH:34][CH:33]=2)=[N:24]1.O>CS(C)=O>[F:21][C:16]1[C:17]([F:19])=[CH:18][N:14]([C:12]2[CH:11]=[CH:10][C:9]([N:23]3[CH:28]=[C:27]([O:29][CH3:30])[C:26](=[O:31])[C:25]([C:32]4[N:36]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)[N:35]=[CH:34][CH:33]=4)=[N:24]3)=[C:8]([F:7])[CH:13]=2)[CH:15]=1

Participants

5

Reactant 3

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 468487401-[2-fluoro-4-(3,3,4,4-tetrafluoropyrrolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

Product 1

HCID 468489141-[4-(3,4-Difluoro-1H-pyrrol-1-yl)-2-fluorophenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 32.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

KOtBu (236 mg, 2.1 mmol) was added portionwise at room temperature to a solution of 1-[2-fluoro-4-(3,3,4,4-tetrafluoropyrrolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (352 mg, 0.7 mmol) in DMSO (3.5 mL). After stirring for 30 min, the reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was subjected to basic silica gel column chromatography eluting with hexane/AcOEt (1/1-0/1) followed by purification by preparative HPLC. Recrystallization from MeOH/H2O afforded the title compound (105 mg, 32% yield) as a white solid: mp 212-214° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.91 (3H, s), 6.42 (1H, t, J=9.0 Hz), 6.68-6.78 (2H, m), 6.87 (1H, ddd, J=1.1, 2.6, 9.0 Hz), 7.07 (1H, dd, J=2.6, 12.4 Hz), 7.33 (1H, d, J=2.3 Hz), 7.36-7.48 (5H, m), 7.78-7.79 (2H, m). LC-MS (ESI) m/z 464 [M+H]+. Anal. Calcd for C24H16F3N5O2: C, 62.20; H, 3.48; N, 15.11. Found: C, 62.20; H, 3.51; N, 15.01.

Workup

  1. extractionextracted with AcOEt
  2. washThe extract was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. washeluting with hexane/AcOEt (1/1-0/1)
  6. customfollowed by purification by preparative HPLC
  7. customRecrystallization from MeOH/H2O

Sources & evidence

ORD record
ord-b80ef43915d44c0a9a1f7db37dc74964
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

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