3-Amino-5-methylisoxazole → 6-chloro-N-(3-fluoropyridin-4-yl)-8-(5-methylisoxazol-3-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943472

Reaction equation

HRID 1943472 reaction equation
Br[C:2]1[C:3]2[N:4]([C:9]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3[F:21])=[O:13])=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:22][C:23]1[O:27][N:26]=[C:25]([NH2:28])[CH:24]=1.CC(C)([O-])C.[Na+]>C1COCC1>[Cl:8][C:6]1[CH:7]=[C:2]([NH:28][C:25]2[CH:24]=[C:23]([CH3:22])[O:27][N:26]=2)[C:3]2[N:4]([C:9]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[CH:17][C:16]=3[F:21])=[O:13])=[CH:10][N:11]=2)[N:5]=1

Participants

5

Reactant 3

HCID 661723-Amino-5-methylisoxazoleHCID 23676156Sodium t-butoxideHCID 596244958-Bromo-6-chloro-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

Product 1

HCID 866492716-chloro-N-(3-fluoropyridin-4-yl)-8-(5-methylisoxazol-3-ylamino)imidazo[1,2-b]pyridazine-3-carboxamideYield 48.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 5A (40 mg, 0.123 mmol), 5-methylisoxazol-3-amine (30.1 mg, 0.307 mmol) and sodium t-butoxide (29.5 mg, 0.307 mmol) in THF (1.5 mL) was heated at 70° C. for 2 h, the cooled to room temperature. The solvent was removed and the residue was purified by ISCO column chromatography (4 g column, MeOH/DCM=0-10%) to give 51A (23 mg, 48%). HPLC Rt=3.043 min (Chromolith SpeedROD 4.6×50 mm, 10-90% aqueous methanol containing 0.1% TFA, 4 min gradient, monitored at 220 nm), [M+H]=388.

Workup

  1. temperaturethe cooled to room temperature
  2. customThe solvent was removed
  3. customthe residue was purified by ISCO column chromatography (4 g column, MeOH/DCM=0-10%)

Sources & evidence

ORD record
ord-065ce67624804506b21135dc68200e45
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Linked notes

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