p-Toluenesulfonic acid → Methyl 5-((4-((4-aminonaphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-1H-indazole-3-carboxylate

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[C:11]([O:13][CH3:14])=[O:12].[CH3:15][C:16]1[CH:17]=[CH:18][C:19](S(O)(=O)=O)=[CH:20][CH:21]=1.[CH3:26][N:27]([CH:29]=[O:30])C>>[NH2:6][C:5]1[C:17]2[C:16](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:15]([O:30][C:29]2[CH:10]=[CH:2][N:1]=[C:26]([NH:1][C:2]3[CH:3]=[C:4]4[C:8](=[CH:9][CH:10]=3)[NH:7][N:6]=[C:5]4[C:11]([O:13][CH3:14])=[O:12])[N:27]=2)=[CH:3][CH:4]=1

Participants

Reactant 3

HCID 6101p-Toluenesulfonic acid

HCID 6228Dimethylformamide

HCID 28819013Methyl 5-amino-1H-indazole-3-carboxylate

Product 1

HCID 90004981Methyl 5-((4-((4-aminonaphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-1H-indazole-3-carboxylate

Procedure

A solution of Intermediate E2 (1.60 g, 5.90 mmol), methyl 5-amino-1H-indazole-3-carboxylate (1.35 g, 7.07 mmol) and p-TSA (2.24 g, 11.8 mmol) in DMF (30 mL) was stirred at 60° C. for 16 hr. The reaction mixture was cooled to RT and was partitioned between EtOAc (100 mL) and saturated aq. NaHCO3 (100 mL). The layers were separated and the organic extract was washed with water (2×100 mL) and brine (2×100 mL) and then dried and evaporated in vacuo. The residue was purified by trituration with acetonitrile to afford the title compound Intermediate B16 as a brown solid (0.937 g, 87% pure by HPLC, 33%); Rt 1.67 min (Method 2, acidic); m/z 427 (M+H)+ (ES+). The material was used in subsequent steps without additional purification.