反应详情

温度

110 °C

To a solution of tert-butyl 4-((5-(6-chloro-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)amino)piperidine-1-carboxylate (45) (400 mg, 0.9 mmol) in dioxane (10 mL): H2O (2 mL), 6-amino benzothiazole (1.3 mmol, 1.5 equiv.), xanthphos (0.4 mmol, 0.5 equiv.) and Na2CO3 (2.7 mmol, 3 equiv.) were added and degassed for 10 min. To the reaction mixture Pd2(dba)3 (0.4 mmol, 0.5 equiv.) was added and degassed again for 10 min. It was then heated at 110° C. for overnight. The reaction mass was cooled and filtered through small pad of celite. The filtrate obtained was concentrated to provide crude material. The crude material was purified by column chromatography through silica gel and MeOH: DCM as eluent. The material obtained was further purified by prep. HPLC to afford tert-butyl 4-((5-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-oxadiazol-2-yl)amino)piperidine-1-carboxylate. 1H NMR: 400 MHz, CD3OD: δ 1.34 (d, J=6.00 Hz, 6H), 1.48 (s, 9H), 1.58-1.60 (m, 2H), 1.96-2.06 (m, 4H), 3.29-3.34 (2H, merged with the water peak), 3.61-3.64 (m, 1H), 3.78-3.82 (m, 1H), 4.00-4.04 (m, 2H), 6.16 (s, 1H), 7.53-7.58 (m, 2H), 7.97 (d, J=8.80 Hz, 1H), 8.37 (s, 1H), 8.43 (d, J=2.00 Hz, 1H), 9.08 (s, 1H). LC/MS: Purospher@star RP-18, 4×55 mm, 3 μm; Solvent A=10% ACN: 90% H2O: 20 mM NH4OAc; Solvent B=90% ACN: 10% H2O: 20 mM NH4COOAc; gradient 0-100% B over 1.5 min (3.2 min run time); retention time: 2.028 mM; LCMS (ES-API), m/z 551.2 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 7.276 mM; Purity: 98.8%.

1. customdegassed for 10 min
2. customdegassed again for 10 min
3. temperatureThe reaction mass was cooled
4. filtrationfiltered through small pad of celite
5. customThe filtrate obtained
6. concentrationwas concentrated
7. customto provide crude material
8. customThe crude material was purified by column chromatography through silica gel and MeOH
9. customThe material obtained
10. customwas further purified by prep