Diethyl Ether → 2-(3-([7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide

Temperature

0 °C

2,3-difluoroaniline (1.15 g, 8.95 mmol) was added to a suspension of (3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid (2.70 g, 7.46 mmol) in pyridine (30 ml) and the reaction cooled to 0° C. Phosphorous oxychloride (1.14 g, 7.46 mmol) was added dropwise and the reaction stirred at 0° C. for 1 hour. The reaction was warmed to ambient temperature and more phosphorous oxychloride (0.5 ml) added. The reaction was stirred for 4.5 hours. The reaction mixture was diluted with ethyl acetate:ether (100 ml: 37 ml) and stirred for 18 hours. The precipitate was filtered, suspended in water and neutralised with ammonium hydroxide (7%, 15 ml). The resultant yellow suspension was filtered, washed with water and dried (phosphorous pentoxide) to yield 2-(3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)-N-(2,3-difluorophenyl)acetamide as an orange powder (3.15 g, 89% yield):

1. temperatureThe reaction was warmed to ambient temperature
2. stirringThe reaction was stirred for 4.5 hours
3. filtrationThe precipitate was filtered
4. filtrationThe resultant yellow suspension was filtered
5. washwashed with water
6. dry with materialdried (phosphorous pentoxide)

ORD record

ord-a67375358cb1435c9f10ff05801a8c0f

Source dataset

uspto-grants-2008_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07402585B2