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]=1Participants
4
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.
Workup
- customwas partitioned between EtOAc (100 mL) and saturated aq. NaHCO3 (100 mL)
- customThe layers were separated
- extractionthe organic extract
- washwas washed with water (2×100 mL) and brine (2×100 mL)
- customdried
- customevaporated in vacuo
- customThe residue was purified by trituration with acetonitrile
Sources & evidence
- ORD record
- ord-70320be93f9443b7853cf3306d487f4a
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09249125B2
Reaction notes
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