2-Fluoro-5-methylbenzoic acid → N-{4-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide

HRID 589910Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:11]=[CH:12][C:13]3[N:14]([CH:16]=[C:17]([NH2:19])[N:18]=3)[N:15]=2)=[CH:4][CH:3]=1.[F:20][C:21]1[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][C:22]=1[C:23](O)=[O:24].Cl.CN(C)CCCN=C=NCC>ClC(Cl)C.CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[NH2:19][C:17]1[N:18]=[C:13]2[CH:12]=[CH:11][C:10]([C:9]#[C:8][C:5]3[CH:6]=[CH:7][C:2]([NH:1][C:23](=[O:24])[C:22]4[CH:26]=[C:27]([CH3:30])[CH:28]=[CH:29][C:21]=4[F:20])=[CH:3][CH:4]=3)=[N:15][N:14]2[CH:16]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To 6-[(4-aminophenyl)ethynyl]imidazo[1,2-b]pyridazin-2-amine, (30 mg, 0.12 mmol, 1 eq) and 2-fluoro-5-methylbenzoic acid (18.5 mg, 1 eq) in anhydrous dichloroethane (1 mL) under nitrogen atmosphere at room temperature was added 4-(dimethylamino)pyridine (2.94 mg, 0.2 eq) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (27.76 mg, 1.2 eq). After the reaction was stirred at 50° C. for 2 hours, it was diluted with chloroform, washed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine, and lastly dried with anhydrous sodium sulfate. The upper solution was decanted, concentrated, and the solid residue was subject to a gradient column chromatography (from CHCl3 to MeOH—CHCl3 1:25) to yield N-{4-[(2-aminoimidazo[1,2-b]pyridazin-6-yl)ethynyl]phenyl}-2-fluoro-5-methylbenzamide as a yellow solid in amount of 7 mg.

Workup

washwashed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, brine
dry with materiallastly dried with anhydrous sodium sulfate
customThe upper solution was decanted
concentrationconcentrated

Sources & evidence

ORD record: ord-537843567dc94088bfa61cd4ecc89104
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233968B1

Reaction notes

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