反应详情

2-(3-Chloropyrazin-2-yl)-2-methylpropanoic acid, INTERMEDIATE 29 (0.250 g, 1.246 mmol) was dissolved in a mixture of thionyl chloride (5 ml, 68.5 mmol) and dichloromethane (5 mL) and heated to reflux. After 20 minutes the solution was evaporated to dryness under reduced pressure. The crude was dissolved in carbon tetrachloride (20 mL) and evaporated to dryness once more. The crude was dried further under high vac then dissolved in dichloromethane (20 mL). The product was then added to an ice cooled solution of trans-N1-(5-fluorobenzo[d]thiazol-2-yl)cyclobutane-1,3-diamine, in the presence of INTERMEDIATE 73 (0.245 g, 1.032 mmol) and diisopropylethylamine (1.0 ml, 5.75 mmol) in dry tetrahydrofuran (30 mL). The mixture was stirred for 5 minutes then sodium tert-butoxide (0.50 g, 5.20 mmol) was added in one portion and the reaction stirred for an additional 20 minutes. Water (200 mL) and ethyl acetate (300 mL) were added and the phases mixed and separated. The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (dichloromethane to ethyl acetate gradient) gave the desired 5-(trans-3-((5-fluorobenzo[d]thiazol-2-yl)amino)cyclobutyl)-7,7-dimethyl-5H-pyrrolo[2,3-b]pyrazin-6(7H)-one (0.135 g, 0.352 mmol, 34.1% yield) m/z: 384.0 (M+1); 1H NMR (400 MHz, CHLOROFORM-d) δ: ppm 1.46 (s, 6 H) 2.45-2.55 (m, 2 H) 3.40-3.51 (m, 2 H) 4.53-4.63 (m, 1 H) 5.31 (quin, J=8.46 Hz, 1 H) 6.62 (br. s., 1 H) 6.84 (td, J=8.80, 2.15 Hz, 1 H) 7.27 (dd, J=9.98, 2.15 Hz, 1 H) 7.51 (dd, J=8.70, 5.38 Hz, 1 H) 8.11 (dd, J=13.99, 3.03 Hz, 2 H).

1. temperatureheated to reflux
2. customAfter 20 minutes the solution was evaporated to dryness under reduced pressure
3. dissolutionThe crude was dissolved in carbon tetrachloride (20 mL)
4. customevaporated to dryness once more
5. customThe crude was dried further under high vac
6. dissolutionthen dissolved in dichloromethane (20 mL)
7. stirringthe reaction stirred for an additional 20 minutes
8. additionthe phases mixed
9. customseparated
10. dry with materialThe organic was dried with magnesium sulfate
11. customevaporated to dryness under reduced pressure
12. customPurification