Trifluoroacetic acid → HCID 71256152, compound

To a stirred solution of (E)-4-(cyclobutyl(methyl)amino)but-2-enoic acid (139 mg, 0.48 mmol) in acetonitrile (4 mL) was added a drop of DMF before introducing (COCl)2 (73 mg, 0.574 mmol). The resulting mixture was stirred at RT for 2 h. Solvent was removed in vacuo. The residue was dissolved in DCM (5 mL) and the resulting solution was slowly introduced to a pre-cooled solution of tert-butyl-3-iodo-1-(3-(methylamino)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylcarbamate (46) (186 mg, 0.4 mmol) in DCM (5 mL) dropwise. Stirring was continued at RT overnight. TFA (8 mL) was added and resulting reaction mixture was stirred at RT for additional 2 h and then concentrated in vacuo. The residue was dissolved in sat. aqueous NaHCO3. The crude product was extracted with 85% DCM/IPA (50 mL×3). The combined organic extracts were dried over Na2SO4, filtered and concentrated to provide (E)-N-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-4-(cyclobutyl(methyl)amino)-N-methylbut-2-enamide (52) (222 mg, quant. yield) as a white solid. LC-MS (ESI): m/z (M+1) 518.1.

1. customSolvent was removed in vacuo
2. dissolutionThe residue was dissolved in DCM (5 mL)
3. stirringStirring
4. waitwas continued at RT overnight
5. customresulting
6. customreaction mixture
7. stirringwas stirred at RT for additional 2 h
8. concentrationconcentrated in vacuo
9. dissolutionThe residue was dissolved in sat. aqueous NaHCO3
10. extractionThe crude product was extracted with 85% DCM/IPA (50 mL×3)
11. dry with materialThe combined organic extracts were dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated

ORD record

ord-5cc00a2cf0fb4880b927113771913d0d

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08377946B1