Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Toluene | HCID 1140 | — |
| Reactant | Diethyl Ether | HCID 3283 | — |
| Reactant | Phosgene | HCID 6371 | — |
| Reactant | Diisopropylethylamine | HCID 81531 | — |
| Reactant | 4-(4-Amino-2-fluorophenoxy)picolinamide | HCID 23153205 | — |
| Reactant | HCID 56919414 | HCID 56919414 | — |
| Reactant | N-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamide | HCID 59853038 | — |
| Reactant | HCID 178418348 | HCID 178418348 | — |
| Solvent | Dimethylformamide | HCID 6228 | — |
| Solvent | Tetrahydrofuran | HCID 8028 | — |
| Product | HCID 59853008 | HCID 59853008 | 33% |
Reaction Steps
To a solution of 2-(4-fluorophenyl)-N-methylacetamide (89 mg, 0.53 mmol) in 2 mL of THF at −78° C. was added MeLi in Et2O (1.6 M, 0.34 mL, 0.55 mmol). The solution was stirred at −78° C. for 5 min and then 20% phosgene in toluene (1.9 M, 0.29 mL, 0.55 mmol) was introduced quickly. After 2 min, 4-(4-amino-2-fluorophenoxy)picolinamide (Compound B′ of Example 24, 100 mg, 0.40 mmol) was added, followed by the addition of DMF (2 mL) and DIEA (0.4 mL). The reaction mixture was stirred at room temperature for 1 h and quenched with H2O. The solution was then extracted with EtOAc and the organic layer was washed with brine, dried over MgSO4. After filtration and concentration, the residue was purified by silica gel chromatography to give the title compound (77 mg, 33%). MS(ESI+) m/z 441 (M+H)+.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US07459562B2 |
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| Source dataset | uspto-grants-2008_12 |
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| ORD ID | ord-ec628043c22a4e22824d862415d30303 |
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| Source note | uspto-grants-2008_12 |
|---|