Methyl iodide → HCID 71736252, compound

Reaction equation

Cl.N1CC=[C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:11]=[CH:10][C:9]=2[C:18]2[CH:27]=[CH:26][CH:25]=[C:24]3[C:19]=2[CH2:20][CH2:21][N:22]([S:28]([NH:31][C:32]2[S:36][N:35]=[CH:34][N:33]=2)(=[O:30])=[O:29])[CH2:23]3)CC1.C[CH2:38][N:39]([CH:43]([CH3:45])C)[CH:40]([CH3:42])C.I[CH3:47]>C1COCC1>[OH-:29].[S:36]1[C:32]([NH:31][S:28]([N:22]2[CH2:21][CH2:20][C:19]3[C:24](=[CH:25][CH:26]=[CH:27][C:18]=3[C:9]3[CH:10]=[CH:11][C:12]([C:14]([F:17])([F:16])[F:15])=[CH:13][C:8]=3[C:5]3[CH2:45][CH2:43][N+:39]([CH3:38])([CH3:47])[CH2:40][CH:42]=3)[CH2:23]2)(=[O:30])=[O:29])=[N:33][CH:34]=[N:35]1

Participants

Procedure

A solution of 5-(2-(1,2,3,6-tetrahydropyridin-4-yl)-4-(trifluoromethyl)phenyl)-N-(1,2,4-thiadiazol-5-yl)-3,4-dihydroisoquinoline-2(1H)-sulfonamide hydrochloride (Example 6, 0.213 g, 0.382 mmol) and DIPEA (0.333 ml, 1.908 mmol) in 4 mL THF was treated with iodomethane (0.036 ml, 0.573 mmol) and was allowed to stir at room temperature overnight. The reaction mixture was concentrated. Purification of the resulting residue by reverse phase column chromatography [RediSep Gold C-18 50 g, 5 to 60% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] then by normal phase silica gel column chromatography [(0 to 100% EtOAc/MeOH), Interchim (San Pedro, Calif.) 15 micron MeOH stable column] gave 4-(2-(2-(N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-1,2,3,4-tetrahydro isoquinolin-5-yl)-5-(trifluoromethyl)phenyl)-1,1-dimethyl-1,2,3,6-tetrahydropyridin-1-ium hydroxide (0.026 g, 0.047 mmol). [M+H]+=550.0 1H NMR (400 MHz, Acetone-d6) δ ppm: 7.71-7.79 (m, 3H), 7.48 (d, J=7.9 Hz, 1H), 7.14-7.22 (m, 1H), 7.06 (d, J=7.7 Hz, 2H), 5.75 (br. s., 1H), 4.15-4.45 (m, 4H), 3.67-3.84 (m, 2H), 3.55-3.65 (m, 1H), 3.23 (s, 3H), 3.18 (s, 3H), 3.09 (ddd, J=13.0, 9.6, 4.5 Hz, 1H), 2.64-2.75 (m, 1H), 2.51-2.61 (m, 2H), 2.32 (m, J=16.4, 4.4 Hz, 1H)