3-(4-Chloro-2-fluorobenzyl)-N-(1-(4-methoxybenzyl)-5-methyl-1H-pyrazol-3-yl)-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine → Gandotinib

HRID 597863Notes

Reaction equation

[Cl:1][C:2]1[CH:41]=[CH:40][C:5]([CH2:6][C:7]2[N:11]3[N:12]=[C:13]([NH:23][C:24]4[CH:28]=[C:27]([CH3:29])[N:26](CC5C=CC(OC)=CC=5)[N:25]=4)[CH:14]=[C:15]([CH2:16][N:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)[C:10]3=[N:9][C:8]=2[CH3:39])=[C:4]([F:42])[CH:3]=1>FC(F)(F)C(O)=O>[Cl:1][C:2]1[CH:41]=[CH:40][C:5]([CH2:6][C:7]2[N:11]3[N:12]=[C:13]([NH:23][C:24]4[CH:28]=[C:27]([CH3:29])[NH:26][N:25]=4)[CH:14]=[C:15]([CH2:16][N:17]4[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)[C:10]3=[N:9][C:8]=2[CH3:39])=[C:4]([F:42])[CH:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Combine 3-(4-chloro-2-fluorobenzyl)-N-(1-(4-methoxybenzyl)-5-methyl-1H-pyrazol-3-yl)-2-methyl-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine (0.447 g, 0.76 mmol) and trifluoroacetic acid (10 mL) in a 20 mL microwave reactor tube. Seal with a crimp cap then heat in a microwave reactor at 120° C. for 20 min. Partition between EA and water that is made basic with excess NaOH aqueous. Wash the organic phase three times with NaOH aqueous followed by aqueous saturated sodium chloride. Dry over anhydrous magnesium sulfate. Filter and concentrate in vacuo. Purify on silica gel (EA→10% methanol:EA) to give the title compound (0.246 g, 0.52 mmol) as a pale yellow solid. LCMS (8 min)=470.0, M+1.

Workup

customSeal with a crimp
customcap
customPartition between EA and water that
washWash the organic phase three times with NaOH aqueous
dry with materialDry over anhydrous magnesium sulfate
filtrationFilter
concentrationconcentrate in vacuo
customPurify on silica gel (EA→10% methanol:EA)

Sources & evidence

ORD record: ord-4ce52b383c0a4aceae0f44e288fff9f7
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07897600B2

Reaction notes

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