Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Methylamine | HCID 6329 | — |
| Reactant | Lithium Hexamethyldisilazide | HCID 2733832 | — |
| Reactant | HCID 86687494 | HCID 86687494 | — |
| Catalyst | Dicyclohexyl(2 inverted exclamation mark,4 inverted exclamation mark,6 inverted exclamation mark-Triisopropyl-3,6-Dimethoxy-[1,1 inverted exclamation mark-Biphenyl]-2-Yl)Phosphine-(2-(2-Aminoethyl)Phenyl)Palladium(Ii) Chloride | HCID 75412134 | — |
| Solvent | Methanol | HCID 887 | — |
| Product | HCID 86687497 | HCID 86687497 | 85.3% |
Reaction Steps
A vial was charged with 3-chloro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Example 249) (34.13 mg, 0.068 mmol) and chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(ii) (Strem Chemical, Newburyport, Mass.) (5.45 mg, 6.83 μmol), then flushed with Ar (g). Methanamine (2M in THF) (341 μl, 0.683 mmol) was added to give a solution. Lithium bis(trimethylsilyl)amide (1M in THF) (341 μl, 0.341 mmol) was added, resulting in the formation of a maroon solution. After 15 min, the mixture was diluted with MeOH and concentrated. The residue was purified by chromatography on silica gel (12-g column, 0 to 10% MeOH/DCM) to give 1-(2-methoxy-4-(trifluoromethyl)phenyl)-3-(methylamino)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (28.58 mg, 0.058 mmol, 85% yield) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm=12.81 (br. s., 1H), 8.11 (d, J=1.6 Hz, 1H), 7.53-7.42 (m, 3H), 7.36-7.24 (m, 3H), 6.88-6.82 (m, 1H), 6.79-6.71 (m, 2H), 3.75 (s, 3H), 2.82 (d, J=5.0 Hz, 3H); m/z (ESI) 495.2 (M+H)+.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US09012443B2 |
|---|
| Source dataset | uspto-grants-2015_04 |
|---|
| ORD ID | ord-e40f359248714deb9b913093b5cccfb2 |
|---|
| Source note | uspto-grants-2015_04 |
|---|
