Hydrochloric Acid → 3-[3-[4-(2-Aminothiazol-4-yl)-4-phenylpiperid-1-yl]propyl]-1-benzoyl-3-(3,4-dichlorophenyl)piperidine dihydrochloride monohydrate

HRID 50061

Reaction equation

HRID 50061 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[N:6]=1.[ClH:19].[C:20]([N:28]1[CH2:33][CH2:32][CH2:31][C:30]([C:50]2[CH:55]=[CH:54][C:53]([Cl:56])=[C:52]([Cl:57])[CH:51]=2)([CH2:34][CH2:35][CH2:36]N2CCC(C(N3CCCC3)=O)CC2)[CH2:29]1)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.C(#N)C>[OH2:27].[ClH:56].[ClH:19].[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:7]2([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:8][CH2:9][N:10]([CH2:36][CH2:35][CH2:34][C:30]3([C:50]4[CH:55]=[CH:54][C:53]([Cl:56])=[C:52]([Cl:57])[CH:51]=4)[CH2:31][CH2:32][CH2:33][N:28]([C:20](=[O:27])[C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:29]3)[CH2:11][CH2:12]2)[N:6]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 227417141-Benzoyl-3-(3,4-dichlorophenyl)-3-[3-[4-(pyrrolidin-1-ylcarbonyl)piperid-1-yl]propyl]piperidine hydrochlorideHCID 227417264-(2-Aminothiazol-4-yl)-4-phenylpiperidine

Product 1

HCID 227417843-[3-[4-(2-Aminothiazol-4-yl)-4-phenylpiperid-1-yl]propyl]-1-benzoyl-3-(3,4-dichlorophenyl)piperidine dihydrochloride monohydrateYield 104.5%

Reagents, catalysts & solvents 1

HCID 21891449acetonitrile N,N-dimethylformamideSolvent

Procedure

A mixture of 1.04 g of 4-(2-aminothiazol-4-yl)-4-phenylpiperidine (compound of PREPARATION 1.4 in the form of the free base), 1.88 g of the compound obtained in step B of EXAMPLE 1 and 1.1 g of K2CO3 in 20 ml of a DMF/acetonitrile mixture (50/50; v/v) is refluxed for 2 hours. The reaction mixture is concentrated under vacuum, the residue is taken up with water and extracted with AcOEt, the organic phase is washed with water and dried over MgSO4 and the solvent is evaporated off under vacuum. The residue is chromatographed on silica using a gradient of a DCM/MeOH mixture (98/2; v/v to 95/5; v/v) as the eluent. The product obtained is taken up with ethereal hydrogen chloride and the precipitate formed is filtered off to give 1.2 g of the expected product after crystallization from AcOEt, m.p.=162-164° C.

Workup

  1. temperatureis refluxed for 2 hours
  2. concentrationThe reaction mixture is concentrated under vacuum
  3. extractionextracted with AcOEt
  4. washthe organic phase is washed with water
  5. dry with materialdried over MgSO4
  6. customthe solvent is evaporated off under vacuum
  7. customThe residue is chromatographed on silica using a gradient of a DCM/MeOH mixture (98/2; v/v to 95/5; v/v) as the eluent
  8. customThe product obtained
  9. customthe precipitate formed
  10. filtrationis filtered off

Sources & evidence

ORD record
ord-ee5f356ebd0548c0862e806cfe07b167
Source dataset
uspto-grants-2004_03
Patent number
US06710042B2

Linked notes

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