Dimethylformamide → HCID 87466312, compound

HRID 2239843Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

In a 250 ml round bottom flask, under a nitrogen atmosphere, was added 8-bromo-6-chloroimidazo[1,2-b]pyridazine (5.0 g, 18.6 mmol) from Example I(1), step 1b, tert-butyl 4-aminobenzoate (3.95 g, 20.5 mmol), and DMF (30 ml). The solution was cooled to 0° C. and 1.0 M potassium tert-butoxide in THF (46 ml) was added dropwise via syringe over 30 minutes. The reaction was allowed to stir at room temperature for 30 minutes and then warmed to 50° C. for 2 hrs and then concentrated in vacuo to remove THF. The resulting solution was taken up in ethyl acetate, washed with H2O (3×300 ml) and then brine (1×50 ml). The organic layers were combined, dried over Na2SO4 and filtered. Following solvent evaporation, 6.0 g of crude product was obtained. Further purification was done via triteration with 3:1 diethyl ether/heptane to give 2.2 g of tert-butyl 4-(6-chloroimidazo[1,2-b]pyridazin-8-ylamino)benzoate as a brown solid after filtration.

Workup

temperaturewarmed to 50° C. for 2 hrs
concentrationconcentrated in vacuo
customto remove THF
washwashed with H2O (3×300 ml)
dry with materialdried over Na2SO4
filtrationfiltered
customFollowing solvent evaporation
custom6.0 g of crude product was obtained
customFurther purification

Sources & evidence

ORD record: ord-198b220ee8694b80be22d3ca31be3456
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07723336B2

Reaction notes

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