Methyl iodide → HCID 71736252, compound

HRID 2172308Notes

Reaction equation

HRID 2172308 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

5

Reactant 3

HCID 6328Methyl iodideHCID 81531DiisopropylethylamineHCID 89815145HCID 89815145, compound

Product 1

HCID 71736252HCID 71736252, compoundYield 24.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

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)

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customPurification 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]

Sources & evidence

ORD record
ord-8558be4ad4c9431fa8dc0d47faef7d55
Source dataset
uspto-grants-2015_06
Patent number
US09051311B2

Reaction notes

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