HuagongsheHuagongshe Chemistry Print Report · For research reference only
Diisopropylethylamine → N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide
Participants
| Role | Name | HCID | Charge |
|---|---|---|---|
| Reactant | Diisopropylethylamine | HCID 81531 | — |
| Reactant | Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) | HCID 9886157 | — |
| Reactant | 2,2-Difluoropropane-1,3-diamine | HCID 19902652 | — |
| Reactant | 4-Fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid | HCID 22019056 | — |
| Solvent | Dimethylformamide | HCID 6228 | — |
| Solvent | Dichloromethane | HCID 6344 | — |
| Solvent | Tetrahydrofuran | HCID 8028 | — |
| Product | N-(3-Amino-2,2-difluoro-propyl)-4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzamide | HCID 22019140 | 65% |
Reaction Steps
To a mixture of 4-fluoro-3-{[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}-benzoic acid (compound 52A, 21 mg, 0.06 mmol) and HATU (38 mg, 0.1 mmol) in DMF (0.2 ml) and THF (0.4 ml), were added 2,2-difluoro-1,3-propanediamine (ref. Tetrahedron, 8617, 1994) (60 mg, 0.54 mmol) and DIPEA (26 mg, 0.2 mmol). The resulting mixture was stirred at RT for 18 h, then diluted with CH2Cl2, washed with brine, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography [silica gel, 5% (NH3/MeOH(2M) in EtOAc] to afford the title compound (17 mg, 65%) as a white solid. LC/MS; (M+H)+=437.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|---|
| Patent number | US07547711B2 |
| Source dataset | uspto-grants-2009_06 |
| ORD ID | ord-7913a66cfb9b4b26b68b10f5cc238c4e |
| Source note | uspto-grants-2009_06 |