Methanol → 6-chloro-N-(3-fluoropyridin-4-yl)-8-(1-methyl-1H-pyrazol-3-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943425Notes

Reaction equation

HRID 1943425 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][C:4]([NH2:7])=[N:3]1.[H-].[Na+].Br[C:11]1[C:12]2[N:13]([C:18]([C:21]([NH:23][C:24]3[CH:29]=[CH:28][N:27]=[CH:26][C:25]=3[F:30])=[O:22])=[CH:19][N:20]=2)[N:14]=[C:15]([Cl:17])[CH:16]=1.CO>CN(C=O)C>[Cl:17][C:15]1[CH:16]=[C:11]([NH:7][C:4]2[CH:5]=[CH:6][N:2]([CH3:1])[N:3]=2)[C:12]2[N:13]([C:18]([C:21]([NH:23][C:24]3[CH:29]=[CH:28][N:27]=[CH:26][C:25]=3[F:30])=[O:22])=[CH:19][N:20]=2)[N:14]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 24758Sodium hydrideHCID 1372541-Methyl-3-aminopyrazoleHCID 596244958-Bromo-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

Product 1

HCID 596247206-chloro-N-(3-fluoropyridin-4-yl)-8-(1-methyl-1H-pyrazol-3-ylamino)imidazo[1,2-b]pyridazine-3-carboxamideYield 43.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-methyl-1H-pyrazol-3-amine (37.2 mg, 0.383 mmol) in DMF (0.8 mL) was added 60% NaH (14.10 mg, 0.353 mmol). The mixture was stirred for 10 min. Solid 8A (50 mg, 0.153 mmol) was added in one portion. The reaction mixture was stirred at room temperature for 3 h. Methanol (5 mL) was added and a solid precipitated that was collected by filtration and dried to give 18A (26 mg, 37%) as an off white solid. [M+H]=387. HPLC Peak Rt=2.753 minutes. (Chromolith column 4.6×50 mm eluting with 10-90% aqueous methanol over 4 minutes containing 0.1% TFA, 4 mL/min, monitoring at 254 nm.)

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 3 h
  2. customa solid precipitated that
  3. filtrationwas collected by filtration
  4. customdried

Sources & evidence

ORD record
ord-b8ebbba9c4d8421da8cf5d6f17387dc2
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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