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

Temperatur

110 °C

A stirred mixture of (1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (50 mg, 0.109 mmol) from Example 29, tributyl(1-ethoxyvinyl)tin (79 mg, 0.218 mmol) and TEA (22 mg, 0.218 mmol) in anhydrous DMF (1 mL) at rt was flushed with a stream of argon for 15 min. To the resulting mixture was added tetrakis(triphenylphosphine)palladium (0) (19 mg, 0.0165 mmol). The reaction vessel was sealed and the mixture was heated with stirring at 110° C. for 1.5 h. After cooling to rt, aq 2 M HCl (500 μL) was added and the mixture was stirred for 1 h. The reaction mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford 1-(3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]thiazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridin-6-yl)ethanone (8 mg, 17%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 9.00 (d, J=1.5 Hz, 1H), 8.76 (s, 1H), 8.64 (s, 1H), 7.99 (d, J=7.5 Hz, 1H), 7.68 (s, 1H), 7.20-7.32 (m, 2H), 5.53 (s, 2H), 4.76 (br s, 1H), 3.50 (m, 1H), 3.30 (m, 1H), 2.68 (s, 3H), 2.04 (m, 1H), 1.87 (m, 1H), 1.55-1.65 (m, 2H), 1.10-1.30 (m, 4H). LCMS (ESI) m/z 422 (M+H)+.

1. customwas flushed with a stream of argon for 15 min
2. customThe reaction vessel was sealed
3. temperaturethe mixture was heated
4. temperatureAfter cooling to rt
5. stirringthe mixture was stirred for 1 h
6. customThe reaction mixture was purified directly by reverse-phase
7. additiona mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase

ORD-Eintrag

ord-8b0c056541a846fb928669549d690632

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08952058B2