Sodium Carbonate → tert-butyl (R)-2-((4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)pyrrolidine-1-carboxylate

温度

80 °C

Into a 100 mL, 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed tert-butyl (2R)-2-([4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl)pyrrolidine-1-carboxylate (380 mg, 0.86 mmol, 1.00 equiv), (2-fluoro-4-phenoxyphenyl)boronic acid (240 mg, 1.03 mmol, 1.20 equiv), tetrakis-(triphenylphosphane) palladium (60 mg, 0.05 mmol, 0.06 equiv), dioxane (50 mL), sodium carbonate (228 mg, 2.15 mmol, 2.50 equiv) and water (10 mL). The resulting solution was stirred for 12 h at 80° C. in an oil bath. The resulting mixture was concentrated under vacuum and the resulting solution was extracted with dichloromethane and the organic layers combined, dried and concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (50/1) to give 0.347 g (80%) of tert-butyl (2R)-2-[[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl]pyrrolidine-1-carboxylate as a brown solid.

1. customInto a 100 mL, 3-necked round-bottom flask purged
2. temperaturemaintained under an inert atmosphere of nitrogen
3. concentrationThe resulting mixture was concentrated under vacuum
4. extractionthe resulting solution was extracted with dichloromethane
5. customdried
6. concentrationconcentrated under vacuum
7. washeluted with dichloromethane/methanol (50/1)

ORDレコード

ord-ee2d2fa83a284a2bbbf433bacca458b0

出典データセット

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09090621B2