1,2-Dimethoxyethane → 4-(6-Butylamino-imidazo[1,2-b]pyridazin-3-yl)-3-fluoro-benzaldehyde

HRID 870650Notes

Reaction equation

Br[C:2]1[N:6]2[N:7]=[C:8]([NH:11][CH2:12][CH2:13][CH2:14][CH3:15])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[F:16][C:17]1[CH:22]=[C:21]([CH:23]=[O:24])[CH:20]=[CH:19][C:18]=1B(O)O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COCCOC>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[CH2:12]([NH:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:18]3[CH:19]=[CH:20][C:21]([CH:23]=[O:24])=[CH:22][C:17]=3[F:16])=[CH:3][N:4]=2)[N:7]=1)[CH2:13][CH2:14][CH3:15]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (810 mg, 3.0 mmol), 2-fluoro-4-formylphenylboronic acid (1.2 g, 7.5 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (200 mg, 0.30 mmol), potassium phosphate (1.9 g, 9.0 mmol), DME (9 mL) and H2O (3 mL) was maintained in a sealed vessel at 80° C. for 12 h. The organic layer was separated and concentrated under reduced pressure to afford a yellow solid that was purified by reverse phase HPLC to afford 4-(6-butylamino-imidazo[1,2-b]pyridazin-3-yl)-3-fluoro-benzaldehyde (600 mg, 64%) as a white solid: 1H NMR (400 MHz, CDCl3) δ ppm 10.02 (d, J=1.8 Hz, 1H), 8.84-8.93 (m, 1H), 8.12 (d, J=4.3 Hz, 1H), 7.79 (dd, J=8.1, 1.5 Hz, 1H), 7.68-7.76 (m, 2H), 6.55 (d, J=9.6 Hz, 1H), 3.43 (td, J=7.1, 5.6 Hz, 2H), 1.67-1.78 (m, 2H), 1.49 (dq, J=15.0, 7.4 Hz, 2H), 1.01 (t, J=7.3 Hz, 3H); LCMS (ESI) m/e 313.1 [(M+H)+, calcd for C17H18FN4O 313.1].

Workup

customThe organic layer was separated
concentrationconcentrated under reduced pressure
customto afford a yellow solid
customthat was purified by reverse phase HPLC

Sources & evidence

ORD record: ord-f1d33c0ee6364862944490f891729eca
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969565B2

Reaction notes

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