1,2-Dichloro-4-isothiocyanatobenzene → N-(3,4-Dichlorophenyl)-4-[(1-methylpiperidin-3-yl)methyl]piperazine-1-carbothioamide

HRID 603171Notes

Reaction equation

HRID 603171 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH2:5][CH:4]([CH2:8][N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH2:3]1.C[Si]([NH-])(C)C.[Na+].[Cl:21][C:22]1[CH:23]=[C:24]([N:29]=[C:30]=[S:31])[CH:25]=[CH:26][C:27]=1[Cl:28]>C(Cl)(Cl)Cl.C1COCC1>[Cl:21][C:22]1[CH:23]=[C:24]([NH:29][C:30]([N:12]2[CH2:13][CH2:14][N:9]([CH2:8][CH:4]3[CH2:5][CH2:6][CH2:7][N:2]([CH3:1])[CH2:3]3)[CH2:10][CH2:11]2)=[S:31])[CH:25]=[CH:26][C:27]=1[Cl:28]

Participants

6

Reactant 3

HCID 230651,2-Dichloro-4-isothiocyanatobenzeneHCID 27369401-[(1-Methylpiperidin-3-yl)methyl]piperazineHCID 23692414Sodium trimethylsilylamide

Product 1

HCID 57656911N-(3,4-Dichlorophenyl)-4-[(1-methylpiperidin-3-yl)methyl]piperazine-1-carbothioamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[(1-methylpiperidin-3-yl)methyl]piperazine (400 mg) in chloroform (10 ml) was added a 2M solution of sodium(trimethylsilyl)amide in THF (2.2 ml). The resulting solution was stirred at room temperature for 10 minutes. 3,4-Dichlorophenylisothiocyanate (0.44 ml) was added and mixture stirred at room temperature for 1 hour. The reaction was quench with water (1 ml) then concentrated in vacuo before being separated between ethyl acetate (100 ml) and saturated sodium bicarbonate solution (100 ml). The ethyl acetate layer was separated, dried over magnesium sulphate, filtered then concentrated in vacuo onto silica gel (1.0 g). The resulting powder was purified by column chromatography on silica gel (50 g) using a gradient of 100% dichloromethane through to 10% methanolic ammonia in dichloromethane to give the title compound (726 mg).

Workup

  1. stirringmixture stirred at room temperature for 1 hour
  2. customThe reaction was quench with water (1 ml)
  3. concentrationthen concentrated in vacuo
  4. custombefore being separated between ethyl acetate (100 ml) and saturated sodium bicarbonate solution (100 ml)
  5. customThe ethyl acetate layer was separated
  6. dry with materialdried over magnesium sulphate
  7. filtrationfiltered
  8. concentrationthen concentrated in vacuo onto silica gel (1.0 g)
  9. customThe resulting powder was purified by column chromatography on silica gel (50 g)

Sources & evidence

ORD record
ord-d978f6ca656e4f4889cff30c9f95199b
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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