Triethylamine → HCID 66836019, compound

HRID 2404484Notes

Reaction equation

HRID 2404484 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([O:19][CH:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1)[C:11]1[CH:12]=[C:13]([CH2:17]O)[CH:14]=[CH:15][CH:16]=1.C(N(CC)CC)C.[CH3:34][S:35](Cl)(=O)=O.C[S-].[Na+]>ClCCl.O.CO>[CH3:26][N:23]1[CH2:24][CH2:25][CH:20]([O:19][CH:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH2:17][S:35][CH3:34])[CH:12]=2)[C:2]2[NH:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[CH2:21][CH2:22]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 4378561Sodium methanethiolateHCID 66835730HCID 66835730, compound

Product 1

HCID 66836019HCID 66836019, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of {3-[(1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenyl}methanol (example 528B, 320 mg) in dichloromethane (3 mL) is added triethylamine (0.16 mL). The reaction mixture is cooled to 0° C., and methanesulfonyl chloride (84 μL) is added dropwise. The reaction mixture is stirred at room temperature for 3 h, then cooled to 0° C. and sodium thiomethoxide (191 mg) is added. After one night at room temperature, methanol (2 mL) is added to help solubilizing the suspension. The reaction mixture is stirred at room temperature overnight. Water is added and the aqueous phase is extracted by dichloromethane. The organic phase is washed by water, then dried over magnesium sulfate and concentrated. The residue is purified by chromatography on silica gel (gradient dichloromethane/methanol/ammonia from 90/10/0 to 90/10/0.1 then 80/20/0.1), followed by a purification by preparative thin-layer chromatography (dichloromethane/methanol/ammonia from 90/10/0.1) to give 2-[(1-methylpiperidin-4-yloxy)(3-methylsulfanylmethylphenyl)methyl]-1H-benzimidazole. MS, [M+H]+=382.1;

Workup

  1. temperaturecooled to 0° C.
  2. waitAfter one night at room temperature
  3. stirringThe reaction mixture is stirred at room temperature overnight
  4. extractionthe aqueous phase is extracted by dichloromethane
  5. washThe organic phase is washed by water
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe residue is purified by chromatography on silica gel (gradient dichloromethane/methanol/ammonia from 90/10/0 to 90/10/0.1
  9. custom80/20/0.1), followed by a purification by preparative thin-layer chromatography (dichloromethane/methanol/ammonia from 90/10/0.1)

Sources & evidence

ORD record
ord-cb398f25cda24adbb99f979f0377c731
Source dataset
uspto-grants-2014_08
Patent number
US08802664B2

Reaction notes

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