N-methyl-2-pyrrolidone → 4-[4-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-5H-pyrrolo[3,2-d]pyrimidin-6-yl]benzoic acid hydrochloride

Temperatur

140 °C

A mixture of ethyl 4-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-6-yl)benzoate hydrochloride (517 mg), 3-chloro-4-[(3-fluorobenzyl)oxy]aniline (462 mg) and 1-methyl-2-pyrrolidinone (8 mL) was stirred at 140° C. for 5 hrs, poured into water (40 mL), and adjusted to pH 8 with saturated aqueous sodium hydrogen carbonate. The precipitated solid was collected by filtration, washed with water and suspended in methanol (15 mL). After stirring at room temperature for 30 min, the solid was collected by filtration and dried under reduced pressure at 60° C. The obtained solid was suspended in ethanol (10 mL) and 1N aqueous sodium hydroxide solution (1.5 mL) was added. After stirring at room temperature for 6.5 hrs, and at 60° C. for 3.5 hrs, the mixture was cooled to room temperature. 1N Hydrochloric acid (155 mL) was added, and the precipitated solid was collected by filtration, washed with water and dried under reduced pressure at 60° C. to give the title compound (498 mg).

1. filtrationThe precipitated solid was collected by filtration
2. washwashed with water
3. stirringAfter stirring at room temperature for 30 min
4. filtrationthe solid was collected by filtration
5. customdried under reduced pressure at 60° C
6. addition1N aqueous sodium hydroxide solution (1.5 mL) was added
7. stirringAfter stirring at room temperature for 6.5 hrs
8. waitat 60° C. for 3.5 hrs
9. temperaturethe mixture was cooled to room temperature
10. addition1N Hydrochloric acid (155 mL) was added
11. filtrationthe precipitated solid was collected by filtration
12. washwashed with water
13. customdried under reduced pressure at 60° C.

ORD-Eintrag

ord-5359cf9495684a5db3b9d56e610b38ce

Quelldatensatz

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08178543B2