Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Hydrochloric Acid | HCID 313 | — |
| Reactant | Methanol | HCID 887 | — |
| Reactant | 5-Isothiocyanato-3-(trifluoromethyl)pyridine-2-carbonitrile | HCID 25019980 | — |
| Reactant | 4-[(1-Cyanocyclobutyl)amino]-2-fluoro-N-methylbenzamide | HCID 44139520 | — |
| Solvent | Dimethylformamide | HCID 6228 | — |
| Product | Apalutamide | HCID 24872560 | 35% |
Reaction Steps
5-isothiocyanato-3-(trifluoromethyl)pyridine-2-carbonitrile, 9, A is reacted with 4-(1-cyanocyclobutylamino)-2-fluoro-N-methylbenzamide B in DMF solution by heating in a microwave at 80° C. for 20 hours. Methanol and hydrochloric acid are then added and the reaction allowed to proceed for 2 hours to produce 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-5-yl)-2-fluoro-N-methylbenzamide, A52 (yield 35 to 87%).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US09388159B2 |
|---|
| Source dataset | uspto-grants-2016_07 |
|---|
| ORD ID | ord-56c49c0e41844024838ea9b57f603c16 |
|---|
| Source note | uspto-grants-2016_07 |
|---|
