Reaction equation
[I:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:13])=[O:12])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[Cl:16][C:17]1[CH:22]=[C:21](Cl)[N:20]=[C:19]([NH2:24])[N:18]=1>CN(C=O)C>[NH2:24][C:19]1[N:20]=[C:21]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([I:1])[CH:10]=3)[C:6]([C:11]([OH:13])=[O:12])=[N:7]2)[CH:22]=[C:17]([Cl:16])[N:18]=1Participants
Procedure
To a solution of 6-iodo-1H-indazole-3-carboxylic acid (3.00 g, 10.42 mmol) in dry DMF (50 mL) at 0° C. under an atmosphere of nitrogen was introduced sodium hydride (1.25 g of a 60% dispersion in mineral oil, 31.25 mmol). The reaction mixture was warmed to RT for 15 mins. 4,6-Dichloropyrimidin-2-amine (2.56 g, 15.62 mmol) was then added, and the solution warmed to 60° C. for 18 hr. After cooling to 0° C., the reaction was carefully quenched with water (50 mL) and acidified by addition of 0.5M aqueous citric acid. The resulting precipitate was collected by filtration, washed on the filter with 1:1 methanol/EtOAc and dried under vacuum to furnish the title compound as a beige solid: LC-MS: m/z=+415.85/417.90 (M+H)+. This compound, with LC-MS purity=70% UV, was used in the next step without further purification.
Workup
- temperaturethe solution warmed to 60° C. for 18 hr
- temperatureAfter cooling to 0° C.
- customthe reaction was carefully quenched with water (50 mL)
- additionacidified by addition of 0.5M aqueous citric acid
- filtrationThe resulting precipitate was collected by filtration
- washwashed on the
- filtrationfilter with 1:1 methanol/EtOAc
- customdried under vacuum
Sources & evidence
- ORD record
- ord-2d89aab53fac448c93e5dfd5aee10e6b
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08901313B2
Linked notes
Loading…