Sodium Hydroxide → N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-1,3-dimethyl-1H-pyrazole-4-carboxamide

HRID 1667979Notes

Reaction equation

HRID 1667979 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5]([C:7](O)=[O:8])[C:4]([CH3:10])=[N:3]1.C(Cl)(=O)C(Cl)=O.[NH2:17][C:18]1[CH:19]=[C:20]([CH:37]=[CH:38][CH:39]=1)[O:21][C:22]1[CH:23]=[CH:24][C:25]2[N:26]([CH:28]=[C:29]([NH:31][C:32]([CH:34]3[CH2:36][CH2:35]3)=[O:33])[N:30]=2)[N:27]=1.[OH-].[Na+]>ClCCl.CN(C)C=O.CN1CCCC1=O>[CH:34]1([C:32]([NH:31][C:29]2[N:30]=[C:25]3[CH:24]=[CH:23][C:22]([O:21][C:20]4[CH:19]=[C:18]([NH:17][C:7]([C:5]5[C:4]([CH3:10])=[N:3][N:2]([CH3:1])[CH:6]=5)=[O:8])[CH:39]=[CH:38][CH:37]=4)=[N:27][N:26]3[CH:28]=2)=[O:33])[CH2:35][CH2:36]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 12733041,3-dimethyl-1H-pyrazole-4-carboxylic acidHCID 57386059N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide

Product 1

HCID 57505533N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}oxy)phenyl]-1,3-dimethyl-1H-pyrazole-4-carboxamideYield 58.4%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a suspension of 1,3-dimethyl-1H-pyrazole-4-carboxylic acid (140 mg, 1.0 mmol) in dichloromethane (10 mL) were added N,N-dimethylformamide (2 drops) then oxalyl chloride (0.171 mL, 2.0 mmol), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure. The residue was diluted with N-methylpyrrolidone (5 mL), N-[6-(3-aminophenoxy)imidazo[1,2-b]pyridazin-2-yl]cyclopropanecarboxamide (155 mg, 0.50 mmol) was added thereto, and the mixture was stirred at room temperature for 6 hr. To the reaction mixture was added 0.5N aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→70/30). The objective fraction was concentrated under reduced pressure, and the residue was washed with diisopropyl ether to give the title compound (126 mg, yield 58%) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→70/30)
  6. concentrationThe objective fraction was concentrated under reduced pressure
  7. washthe residue was washed with diisopropyl ether

Sources & evidence

ORD record
ord-5d392a34b35f4da29e8923879936a989
Source dataset
uspto-grants-2011_10
Patent number
US08044049B2

Reaction notes

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