1,2-Dichloroethane → 4-[[6-Chloro-3-(4-chloro-2-fluorobenzyl)-2-methylimidazo[1,2-b]pyridazin-8-yl]methyl]morpholine

HRID 597861Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[N:14]3[N:15]=[C:16]([Cl:26])[CH:17]=[C:18]([CH2:19][N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)[C:13]3=[N:12][C:11]=2[CH3:27])O)=[C:4]([F:28])[CH:3]=1.ClCCCl.C([SiH](CC)CC)C.FC(F)(F)C(O)=O>CO>[Cl:26][C:16]1[CH:17]=[C:18]([CH2:19][N:20]2[CH2:21][CH2:22][O:23][CH2:24][CH2:25]2)[C:13]2[N:14]([C:10]([CH2:8][C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=3[F:28])=[C:11]([CH3:27])[N:12]=2)[N:15]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Combine (4-chloro-2-fluorophenyl)(6-chloro-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-3-yl)methanol (0.4 g, 0.94 mmol), 1,2-dichloroethane (25 mL), triethylsilane (0.45 mL, 3 equiv.), and trifluoroacetic acid (0.57 mL, 8 equiv.) in a round bottom flask and place under nitrogen. Heat at 70° C. overnight. Concentrate reaction in vacuo. Load onto a Varian MegaElut® 10 gram SCX ion exchange cartridge (prewashed with methanol). Elute with methanol to remove non-basic impurities. Elute with 2 M ammonia in methanol. Concentrate in vacuo to give the title compound (0.36 g, 94%). LCMS (4 min)=409.0, 411.0, M+1.

Workup

concentrationConcentrate
customreaction in vacuo
washElute with methanol
customto remove non-basic impurities
washElute with 2 M ammonia in methanol
concentrationConcentrate in vacuo

Sources & evidence

ORD record: ord-e06663ce07594b29ad2d28c4e7edaa10
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07897600B2

Reaction notes

Loading…