Isobutylamine → (Rac)-(6-isobutylamino-imidazo[1,2-b]pyridazin-3-yl)-quinolin-6-yl-methanol

HRID 69175Notes

Reaction equation

Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[CH:18][CH:17]=[CH:16]4)[OH:12])=[CH:9][N:10]=2)[N:7]=1.[F-].[K+].[CH2:25]([NH2:29])[CH:26]([CH3:28])[CH3:27]>CN1C(=O)CCC1.CC(OC)(C)C>[CH2:25]([NH:29][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[C:15]4[C:20](=[CH:21][CH:22]=3)[N:19]=[CH:18][CH:17]=[CH:16]4)[OH:12])=[CH:9][N:10]=2)[N:7]=1)[CH:26]([CH3:28])[CH3:27]

Participants

Conditions

Temperature: 160 °C

Procedure

(rac)-(6-chloro-imidazo[1,2-b]pyridazin-3-yl)-quinolin-6-yl-methanol (Stage 1.1, 80 mg, 0.257 mmol) and KF (30 mg, 0.515 mmol) were suspended in NMP (2 mL). Isobutylamine (129 μL, 1.287 mmol) was then added and the RM was stirred at 160° C. for 7 h. The mixture was diluted with TBME and washed with water (3×). The aqueous layer was then extracted with TBME (3×). The combined layers were dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (Flashmaster) to afford the title compound as a yellow foam (tR 4.11 min (conditions 4), MH+=348.0, 1H-NMR in DMSO-d6: 8.86 (m, 1H); 8.32 (m, 1H); 8.02 (m, 1H); 7.94 (d, 1H); 7.80 (m, 1H); 7.61 (d, 1H); 7.51 (dd, 1H); 7.31 (s, 1H); 6.88 (t, 1Ht); 6.61 (d, 1H); 6.24 (m, 1H); 6.12 (d, 1H); 2.98 (m, 2H); 1.82 (m, 1H); 0.86 (m, 6H)).

Workup

washwashed with water (3×)
extractionThe aqueous layer was then extracted with TBME (3×)
dry with materialThe combined layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography (Flashmaster)

Sources & evidence

ORD record: ord-8783c27a2cc24dc389f649d4f5c1c640
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822468B2

Reaction notes

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