Phosphorus oxychloride → 4,5-dichloro-N-(1-methyl-1H-pyrazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine

Temperature

70 °C

5-chloro-N-(1-methyl-1H-pyrazol-4-yl)-4-(1-phenylethoxy)-7H-pyrrolo[2,3-d]pyrimidin-2-amine (1.65 g, 4.47 mmol) was suspended in POCl3 (9 mL) and the reaction was heated to 70° C. for 40 min, then further heated to 100° C. for 0.5 hr. The reaction mixture was cooled, concentrated in vacuo and diluted with water (50 mL). NH4OH was added to adjusted the pH 8 and the mixture was extracted with EtOAc (three×75 mL), and concentrated under reduced pressure. A precipitate was formed upon concentrating that was filtered off, and the filtrate was concentrated and the resulting residue was purified by flash chromatography eluting with a gradient of 30% 100% EtOAc in heptanes to afford the title compound (282 mg, 22% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.96 (br. s., 1H) 9.58 (br. s., 1H) 7.87 (s, 1H) 7.52 (s, 1H) 7.37 (s, 1H) 3.81 (s, 3H). m/z (APCI+) for C10H8Cl2N6 283.15 (M+H)+.

1. temperaturefurther heated to 100° C. for 0.5 hr
2. temperatureThe reaction mixture was cooled
3. concentrationconcentrated in vacuo
4. additiondiluted with water (50 mL)
5. additionNH4OH was added
6. extractionthe mixture was extracted with EtOAc (three×75 mL)
7. concentrationconcentrated under reduced pressure
8. customA precipitate was formed
9. concentrationupon concentrating
10. filtrationthat was filtered off
11. concentrationthe filtrate was concentrated
12. customthe resulting residue was purified by flash chromatography
13. washeluting with a gradient of 30% 100% EtOAc in heptanes

ORD record

ord-7f7d4ed7fb684bbe9a8da752e81291a5

Source dataset

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09040547B2