Hydrochloric Acid → 4-(2-(6-Ethoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine
Reaction equation
F[C:2]1[C:7]([C:8]2[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[NH2:16][C:17]1[CH:18]=[CH:19][C:20]([O:23][CH2:24][CH3:25])=[N:21][CH:22]=1.O1CCOCC1.Cl>>[CH2:24]([O:23][C:20]1[N:21]=[CH:22][C:17]([NH:16][C:2]2[C:7]([C:8]3[N:13]=[C:12]([CH3:14])[N:11]=[C:10]([NH2:15])[N:9]=3)=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:18][CH:19]=1)[CH3:25]Participants
Conditions
- Temperature
- 100 °C
Procedure
4-(2-Fluoropyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (0.100 g, 0.49 mmol), 5-amino-2-ethoxypyridine (Combi-Blocks, Inc., San Diego, Calif.), 1,4-dioxane (0.75 mL, 8.8 mmol), (Aldrich, St. Louis, Mo.) and 2 N aqueous HCl (0.24 mL, 0.49mmol) were added to a 50 mL round-bottomed flask. The suspension was stirred at 100° C. overnight. The crude product was adsorbed onto a plug of silica gel and purified by chromatography through a RediSep®, Teledyne ISCO, Lincoln, Nebr., pre-packed silica gel column (40 g), eluting with a gradient of 5% to 20% methanol in dichloromethane to give 4-(2-(6-ethoxypyridin-3-ylamino)pyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine LCMS (API-ES) m/z 324 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 11.80 (br. s., 1H); 8.83 (br. s., 1H); 8.27 (d, J=4.11 Hz, 1H); 8.26 (d, J=4.11 Hz, 1H); 8.11 (br. s., 1H); 7.82 (dd, J=2.93, 1.56 Hz, 1H); 8.81 (d, J=4.11 Hz, 1H); 6.92 (br. s., 1H); 6.86 (d, J=9.39 Hz, 1H); 4.28-4.37 (m, 2H); 2.44 (br. s., 3H); 1.33 (t, J=7.04 Hz, 3H).
Workup
- custompurified by chromatography through a RediSep®, Teledyne ISCO, Lincoln, Nebr
- wash, pre-packed silica gel column (40 g), eluting with a gradient of 5% to 20% methanol in dichloromethane
Sources & evidence
- ORD record
- ord-724d324b97264fc2a543c61a9b496128
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08362241B2
Reaction notes
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