Reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:21]=1.Cl[C:23]1[N:28]=[C:27]([CH3:29])[N:26]=[C:25]([NH2:30])[N:24]=1.CCN(C(C)C)C(C)C>C(O)CCC>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH:14][C:23]3[N:24]=[C:25]([NH2:30])[N:26]=[C:27]([CH3:29])[N:28]=3)[CH3:13])[N:9]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:8]=2[CH:21]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 90 °C
Procedure
A mixture of (S)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (100 mg, 0.31 mmol), 4-chloro-6-methyl-[1,3,5]triazin-2-ylamine (48.4 mg, 0.34 mmol) and DIPEA (0.26 mL, 1.52 mmol) in n-butanol (2 mL) was stirred at 90° C. in a sealed vial for 16 h. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue purified by column chromatography (C18, gradient 20-45% MeOH in 0.5% TFA/H2O) then loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5M NH3/MeOH affording 258 as a white solid (94.2 mg, 85%). LCMS (Method K): RT 3.04 min [M+H]+ 364.1. 1H NMR (DMSO-d6, 400 MHz, 80° C.): δ 7.65 (1H, dd, J=8.7, 4.8 Hz), 7.61-7.57 (2H, m), 7.55-7.51 (3H, m), 7.04 (1H, ddd, J=9.8, 8.7, 2.5 Hz), 6.91 (1H, bs), 6.77 (1H, dd, J=9.0, 2.5 Hz), 6.13 (2H, bs), 5.26 (1H, quintet, J=7.3 Hz), 2.02 (3H, s), 1.44 (3H, d, J=6.9 Hz)
Workup
- temperatureAfter cooling to RT
- customvolatiles were removed under reduced pressure
- customthe resulting residue purified by column chromatography (C18, gradient 20-45% MeOH in 0.5% TFA/H2O)
- washThe cartridge was washed with MeOH
- washthe product eluted with 0.5M NH3/MeOH affording 258 as a white solid (94.2 mg, 85%)
- customRT 3.04 min [M+H]+ 364.1
Sources & evidence
- ORD record
- ord-01f4bbe656044ac2a69aa15f52777fb0
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08653089B2
Linked notes
Loading…