1H-indazol-3-amine → (1H-Indazol-3-yl)-[3-(2-trifluoromethyl-phenyl)-isoquinoline-1-yl]-amine

HRID 133160Notes

Reaction equation

HRID 133160 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]([F:21])([F:20])[F:19])[N:3]=1.[NH:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([NH2:31])=[N:23]1>C(O)C>[NH:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[C:24]([NH:31][C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[CH:5]=[C:4]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:18]([F:21])([F:20])[F:19])[N:3]=2)=[N:23]1

Participants

4

Reactant 2

HCID 133991H-indazol-3-amineHCID 219392261-Chloro-3-(2-trifluoromethyl-phenyl)-isoquinoline

Product 1

HCID 10179350(1H-Indazol-3-yl)-[3-(2-trifluoromethyl-phenyl)-isoquinoline-1-yl]-amineYield 27%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 1-chloro-3-(2-trifluoromethyl-phenyl)-isoquinoline (100 mg, 0.326 mmol) and 1H-indazol-3-ylamine (86 mg, 0.651 mmol) in ethanol (3 mL) was heated at 160 C and the solvent evaporated with a stream of nitrogen. The remaining oil was then heated at 160 C for 18 hours under nitrogen. The resulting melt was dissolved in 5% methanol:dichloromethane (50 mL), washed with saturated aqueous sodium bicarbonate (1×25 mL) then dried over magnesium sulfate. Purification by silica gel chromatography (25% to 50% hexane:ethyl acetate) afforded V-2 as a yellow solid (35 mg, 27%). 1H NMR (500 MHz, d6-DMSO) δ 9.78 (br s, 1H), 8.62 (d, 1H), 7.9–7.85 (m, 1H), 7.78–7.72 (m, 1H), 7.70–7.68 (m, 1H), 7.65–7.62 (m, 1H), 7.60–7.55 (m, 1H), 7.52–7.45 (m, 3H), 7.41–7.38 (m, 1H), 7.28–7.25 (m, 1H), 7.18 (s, 1H), 6.95–6.92 (m, 1H), 5.76 (s, 1H); LC-MS (ES+) m/e=405.18 (M+H); HPLC-Method D Rt 2.74 min.

Workup

  1. customthe solvent evaporated with a stream of nitrogen
  2. temperatureThe remaining oil was then heated at 160 C for 18 hours under nitrogen
  3. dissolutionThe resulting melt was dissolved in 5% methanol
  4. washdichloromethane (50 mL), washed with saturated aqueous sodium bicarbonate (1×25 mL)
  5. dry with materialthen dried over magnesium sulfate
  6. customPurification by silica gel chromatography (25% to 50% hexane:ethyl acetate)

Sources & evidence

ORD record
ord-e725439694a84f819ba6fea9277b7dfa
Source dataset
uspto-grants-2008_06
Patent number
US07390815B2

Reaction notes

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