Dimethylamine → 2-(dimethylamino)-1-(3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)ethanone acetate salt

To a stirred solution of (1R,2R)-2-((6-((6-(1-ethoxyvinyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (90 mg, 0.20 mmol) from the previous step in DMF (2 mL) at 0° C. was added N-bromosuccinimide (36 mg, 0.20 mmol), and the mixture was stirred for 15 min. To the mixture was added dimethylamine (2M in THF, 0.90 mL, 1.80 mmol) and stirring was continued at 0° C. for 5 min. The reaction mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford 2-(dimethylamino)-1-(3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)ethanone acetate salt (5 mg, 5%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.01 (d, J=1.7 Hz, 1H), 8.75 (s, 1H), 8.67 (d, J=1.7 Hz, 1H), 8.03 (d, J=7.5 Hz, 1H), 7.68 (s, 1H), 7.20-7.32 (m, 2H), 5.52 (s, 2H), 4.80 (br s, 1H), 3.78 (s, 2H), 3.51 (br m, 1H), 3.30 (br m, 1H), 2.25 (s, 6H), 2.04 (br m, 1H), 1.82-1.86 (m, 4H), 1.59-1.65 (br m, 2H), 1.10-1.60 (m, 4H); LCMS (ESI) m/z 465 (M+H)+.

1. stirringstirring
2. waitwas continued at 0° C. for 5 min
3. customThe reaction mixture was purified directly by reverse-phase
4. additiona mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase

ORD-Eintrag

ord-f906fe57521d43c9aaebe51e0e7b2751

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08952058B2