Acetyl chloride → N-butyl-3-(isoindolin-5-yl)imidazo[1,2-b]pyridazin-6-amine hydrochloride

HRID 870662Notes

Reaction equation

[CH2:1]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]4)=[CH:13][N:14]=2)[N:11]=1)[CH2:2][CH2:3][CH3:4].C([Cl:34])(=O)C>>[ClH:34].[CH2:1]([NH:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([C:15]3[CH:16]=[C:17]4[C:21](=[CH:22][CH:23]=3)[CH2:20][NH:19][CH2:18]4)=[CH:13][N:14]=2)[N:11]=1)[CH2:2][CH2:3][CH3:4]

Participants

Reactant 2

HCID 6367Acetyl chloride

HCID 86696359Tert-butyl 5-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)isoindoline-2-carboxylate

Product 1

HCID 86696360N-butyl-3-(isoindolin-5-yl)imidazo[1,2-b]pyridazin-6-amine hydrochlorideYield 38.8%

Procedure

The solution of tert-butyl 5-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)isoindoline-2-carboxylate (38 mg, 0.09 mmol) was cooled to 0° C. and treated with acetyl chloride (220 mg, 2.8 mmol). The reaction was maintained at room temperature for overnight. The resulting solution was concentrated under reduced pressure to afford N-butyl-3-(isoindolin-5-yl)imidazo[1,2-b]pyridazin-6-amine hydrochloride (12 mg, 35% yield) as a white solid: 1H NMR (METHANOL-d4) δ: 8.26 (s, 1H), 8.17-8.21 (m, 2H), 7.98 (d, J=10.1 Hz, 1H), 7.65 (d, J=8.6 Hz, 1H), 7.27 (d, J=9.9 Hz, 1H), 4.76 (s, 4H), 3.36-3.45 (m, 2H), 1.63-1.81 (m, 2H), 1.40-1.56 (m, 2H), 1.00 (t, J=7.3 Hz, 3H); LRMS (ESI) m/e 308.4 [(M+H)+, calcd for C18H22N5 308.2].

Workup

concentrationThe resulting solution was concentrated under reduced pressure

Sources & evidence

ORD record: ord-58f934038f774649afdb7e6fb85e2104
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969565B2

Reaction notes

Loading…