p-Toluenesulfonic acid → HCID 90005004, compound

HRID 1771395Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH2:10])=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[CH3:11][C:12]1[CH:13]=[CH:14][C:15](S(O)(=O)=O)=[CH:16][CH:17]=1.[CH3:22][N:23]([CH:25]=[O:26])C>CCOC(C)=O>[NH2:2][C:3]1[C:13]2[C:12](=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:11]([O:26][C:25]2[N:23]=[CH:22][N:1]=[C:9]([NH:10][C:6]3[CH:5]=[C:4]4[C:9](=[CH:8][CH:7]=3)[NH:1][N:2]=[CH:3]4)[CH:8]=2)=[CH:5][CH:4]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A solution of Intermediate E3 (1.50 g, 5.50 mmol), 1H-indazol-5-amine (735 mg, 5.52 mmol) and p-TSA (525 mg, 2.76 mmol) in DMF (14.0 mL) was degassed with nitrogen and was then heated to 60° C. for 16 hr. Additional p-TSA (525 mg, 2.76 mmol) and 1H-indazol-5-amine (368 mg, 2.76 mmol) was added and the reaction maintained at 60° C. for a further 3 hr and then cooled to RT. The resulting mixture was diluted with EtOAc (250 mL) and was washed sequentially with saturated aq. NaHCO3 (2×50 mL), water (2×50 mL) and brine (2×50 mL) and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 120 g, 0-10% [1% NH3 in MeOH] in DCM, gradient elution) to afford the title compound, Intermediate B14, as a dark purple solid (536 mg, 26%); Rt 1.59 min (Method 2, acidic); m/z 369 (M+H)+, (ES+).

Workup

temperaturethe reaction maintained at 60° C. for a further 3 hr
temperaturecooled to RT
washwas washed sequentially with saturated aq. NaHCO3 (2×50 mL), water (2×50 mL) and brine (2×50 mL)
customdried
customevaporated in vacuo
customThe residue was purified by flash column chromatography (SiO2, 120 g, 0-10% [1% NH3 in MeOH] in DCM, gradient elution)

Sources & evidence

ORD record: ord-d6e06f6326e9461fb978ff5edcdf8c90
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249125B2

Reaction notes

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