Trifluoroacetic acid → HCID 71256152, Verbindung

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-Eintrag

ord-45f82fb153774a05855aabfd6e3cec45

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09273051B2