1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-fluoro-N-[4-(imidazo[1,2-b]pyridazin-6-ylethynyl)phenyl]-5-methylbenzamide

HRID 589908Notes

Reaction equation

[N:1]1[CH:2]=[CH:3][N:4]2[C:9]=1[CH:8]=[CH:7][C:6]([C:10]#[C:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][CH:13]=1)=[N:5]2.[F:19][C:20]1[CH:28]=[C:27](C)[CH:26]=[CH:25][C:21]=1[C:22]([OH:24])=O.Cl.[CH3:31]N(C)CCCN=C=NCC>ClC(Cl)C.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[F:19][C:20]1[CH:28]=[CH:27][C:26]([CH3:31])=[CH:25][C:21]=1[C:22]([NH:16][C:15]1[CH:14]=[CH:13][C:12]([C:11]#[C:10][C:6]2[CH:7]=[CH:8][C:9]3[N:4]([CH:3]=[CH:2][N:1]=3)[N:5]=2)=[CH:18][CH:17]=1)=[O:24]

Participants

Conditions

Temperature: 60 °C

Procedure

To the solution of 4-(imidazo[1,2-b]pyridazin-6-ylethynyl)aniline (93.6 mg, 0.4 mmol, 1 eq) and 2-fluoro-4-methylbenzoic acid (62.3 mg, 1 eq) in anhydrous dichloroethane (3 mL) under nitrogen atmosphere at room temperature was added 4-(dimethylamino)pyridine (10 mg, 0.2 eq) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (92.2 mg, 1.2 eq). After the reaction was stirred at 60° C. for 3 hours, it was diluted with ethyl acetate, 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 triturated with EtOAc-Hex (2:1) to yield 2-fluoro-N-[4-(imidazo[1,2-b]pyridazin-6-ylethynyl)phenyl]-5-methylbenzamide as a slightly yellow solid in amount of 122 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
customthe solid residue was triturated with EtOAc-Hex (2:1)

Sources & evidence

ORD record: ord-9ee6e49684f244139f9110f0282568ad
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09233968B1

Reaction notes

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