Hydrochloric Acid → N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)pyridin-2-yl)-1H-indol-4-amine

HRID 1621378Notes

Reaction equation

HRID 1621378 reaction equation
Cl.F[C:3]1[C:8]([C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([NH2:16])[N:10]=2)=[CH:7][CH:6]=[CH:5][N:4]=1.[NH:17]1[C:25]2[CH:24]=[CH:23][CH:22]=[C:21]([NH2:26])[C:20]=2[CH:19]=[CH:18]1.O1CCOCC1>>[NH2:16][C:11]1[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([C:8]2[C:3]([NH:26][C:21]3[C:20]4[CH:19]=[CH:18][NH:17][C:25]=4[CH:24]=[CH:23][CH:22]=3)=[N:4][CH:5]=[CH:6][CH:7]=2)[N:10]=1

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 5834314-AminoindoleHCID 665998524-(2-Fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 49784988N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)pyridin-2-yl)-1H-indol-4-amineYield 22%

Conditions

Temperature
100 °C

Procedure

2N HCl(aq) (0.42 mL, 833 μmol) was added to a stirred mixture of 4-(2-fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (171 mg, 833 μmol) and 1H-indol-4-amine (132 mg, 1000 μmol) in 1,4-dioxane (4.00 mL, 46762 μmol) and the brown mixture was heated at 100° C. overnight. After cooling, the reaction mixture was concentrated and the crude residue was dissolved in DCM/MeOH and mixed with SiO2. The solvent was evaporated and the residue was purified by flash column chromatography (pure DCM to 5% MeOH in DCM) followed by washing the eluent concentrates with EtOAc to give N-(3-(4-amino-6-methyl-1,3,5-triazin-2-yl)pyridin-2-yl)-1H-indol-4-amine (58 mg, 22%) as a yellow solid. LCMS (API-ES) m/z 318 (M+H)+; 1H NMR (400 MHz, d6-DMSO) δ ppm 12.00 (s, 1H) 11.15 (br. s., 1H) 8.77 (dd, J=7.78, 1.76 Hz, 1H) 8.38 (dd, J=4.52, 1.51 Hz, 1H) 8.09 (d, J=6.02 Hz, 1H) 7.53-7.81 (m, 2H) 7.35 (t, J=2.76 Hz, 1H) 6.99-7.19 (m, 2H) 6.90 (dd, J=7.78, 4.77 Hz, 1H) 6.66 (br. s., 1H) 2.55 (s, 3H).

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated
  3. dissolutionthe crude residue was dissolved in DCM/MeOH
  4. additionmixed with SiO2
  5. customThe solvent was evaporated
  6. customthe residue was purified by flash column chromatography (pure DCM to 5% MeOH in DCM)
  7. washby washing the eluent concentrates with EtOAc

Sources & evidence

ORD record
ord-1185f7c741d64b03a707e9e3e1477c0e
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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