HuagongsheHuagongshe Chemistry Print Report · For research reference only
Cyanoacetic acid → 3-[2-[[4-Amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidin-1-yl]-3-oxo-propanenitrile
Participants
| Role | Name | HCID | Charge |
|---|---|---|---|
| Reactant | Cyanoacetic acid | HCID 9740 | — |
| Reactant | Propylphosphonic anhydride | HCID 111923 | — |
| Reactant | 1-(Azetidin-2-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine | HCID 90001212 | — |
| Solvent | Dichloromethane | HCID 6344 | — |
| Product | 3-[2-[[4-Amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidin-1-yl]-3-oxo-propanenitrile | HCID 90001190 | 72% |
Reaction Steps
To a mixture of 1-(azetidin-2-ylmethyl)-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-4-amine (236.4 mg, 0.610 mmol), 2-cyanoacetic acid (77.2 mg, 0.910 mmol) in DCM (8 mL) in ice bath, was added T3P (0.36 mL, 1.21 mmol) and TEA (0.34 mL, 2.42 mmol). The ice bath was removed and the reaction mixture was stirred at room temperature overnight. The reaction mixture was loaded onto the silica gel column, purified with 0-3% gradient MeOH:CH2CL2, to get 3-[2-[[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]azetidin-1-yl]-3-oxo-propanenitrile (201 mg) as yellow oil.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|---|
| Patent number | US09266895B2 |
| Source dataset | uspto-grants-2016_02 |
| ORD ID | ord-541a246e141a4de48a9a9befb3fdd9ac |
| Source note | uspto-grants-2016_02 |