Water → HCID 86646902, compound

HRID 1044508Notes

Reaction equation

HRID 1044508 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([CH:35]=[CH:36][C:37]=1[Cl:38])[CH2:6][CH:7]1[C:16]2[CH:15]=[C:14]([O:17][CH2:18][CH2:19][NH:20][S:21]([C:24]3[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=3)(=[O:23])=[O:22])[CH:13]=[CH:12][C:11]=2[CH2:10][CH2:9][CH:8]1[N:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1.IC.[C:41](=O)([O-])[O-].[Cs+].[Cs+].O>C(#N)C.C(Cl)Cl>[ClH:2].[Cl:2][C:3]1[CH:4]=[C:5]([CH:35]=[CH:36][C:37]=1[Cl:38])[CH2:6][CH:7]1[C:16]2[CH:15]=[C:14]([O:17][CH2:18][CH2:19][N:20]([CH3:41])[S:21]([C:24]3[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=3)(=[O:22])=[O:23])[CH:13]=[CH:12][C:11]=2[CH2:10][CH2:9][CH:8]1[N:30]1[CH2:31][CH2:32][CH2:33][CH2:34]1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodide2×HCID 10796Cesium carbonate2×HCID 57487114HCID 57487114, compound

Product 1

HCID 86646902HCID 86646902, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

N-(2-(8-(3,4-Dichlorobenzyl)-7-(pyrrolidin-1-yl)-5,6,7,8-tetrahydronaphthalen-2-yloxy)ethyl)-1-methyl-1H-pyrazole-4-sulfonamide hydrochloride (41 mg, 0.068 mmol, Example 91, iodomethane (11.6 mg, 0.082 mmol), caesium carbonate (49.0 mg, 0.150 mmol) were dissolved in acetonitrile (3 ml) and stirred for 1 h at 100° C. in the microwave. After addition of another iodomethane (11.6 mg, 0.082 mmol) and caesium carbonate (49.0 mg, 0.150 mmol) it was stirred for another 1 h at 100° C. in the microwave. Water and CH2Cl2 were added, the organic phase separated and the aqueous phase extracted with CH2Cl2. The combined organic layers were washed with saturated NaCl solution, dried over Na2SO4, and concentrated to afford a residue that was purified by flash chromatography (silica gel, MeOH/CH2Cl2 3:97→5:95). The white solid product (42 mg, 38%) was transferred to an HCl salt and precipitated from diisopropyl ether. ESI-MS [M+H+]=577 Calculated for C28H34Cl2N4O3S=576

Workup

  1. stirringwas stirred for another 1 h at 100° C. in the microwave
  2. customthe organic phase separated
  3. extractionthe aqueous phase extracted with CH2Cl2
  4. washThe combined organic layers were washed with saturated NaCl solution
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto afford a residue that
  8. customwas purified by flash chromatography (silica gel, MeOH/CH2Cl2 3:97→5:95)
  9. customprecipitated from diisopropyl ether

Sources & evidence

ORD record
ord-fdca92042362409d996320c1cf7f8f1c
Source dataset
uspto-grants-2013_10
Patent number
US08563617B2

Reaction notes

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