Triethylamine → N-(4-(5-bromopyrrolo[1,2-b]pyridazin-4-yloxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide

HRID 1851088Notes

Reaction equation

HRID 1851088 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][N:5]2[C:10]=1[C:9]([O:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][C:13]=1[F:19])=[CH:8][CH:7]=[N:6]2.[CH3:20][N:21]1[C:25]([CH3:26])=[C:24]([C:27](O)=[O:28])[C:23](=[O:30])[N:22]1[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][N:5]2[C:10]=1[C:9]([O:11][C:12]1[CH:18]=[CH:17][C:15]([NH:16][C:27]([C:24]3[C:23](=[O:30])[N:22]([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:21]([CH3:20])[C:25]=3[CH3:26])=[O:28])=[CH:14][C:13]=1[F:19])=[CH:8][CH:7]=[N:6]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 246564Antipyric acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 583683624-(5-Bromopyrrolo[1,2-b]pyridazin-4-yloxy)-3-fluoroaniline

Product 1

HCID 46193918N-(4-(5-bromopyrrolo[1,2-b]pyridazin-4-yloxy)-3-fluorophenyl)-1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamideYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 4-(5-bromopyrrolo[1,2-b]pyridazin-4-yloxy)-3-fluoroaniline (57 mg, 0.178 mmol) and 1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxylic acid (124 mg, 0.534 mmol) prepared in Preparation Example 1 in dimethylformamide (2 mL), HATU (270 mg, 0.711 mmol) and triethylamine (0.1 mL, 0.711 mmol) were sequentially added and stirred at 50° C. overnight. The resulting reaction mixture was concentrated under reduced pressure and the resulting residue was extracted with dichloromethane and water. The organic layer was separated, dried with magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (10% ethyl acetate in dichloromethane) to give the target compound as a white solid (60 mg, 0.111 mmol, 63% yield).

Workup

  1. customThe resulting reaction mixture
  2. concentrationwas concentrated under reduced pressure
  3. extractionthe resulting residue was extracted with dichloromethane and water
  4. customThe organic layer was separated
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customThe resulting residue was purified by silica gel chromatography (10% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-26ac73716a694d8f84505aca6186c3e6
Source dataset
uspto-grants-2015_02
Patent number
US08957102B2

Reaction notes

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