Hydrochloric Acid → 5-Chloro-2-piperazinyl-n-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-pyridine-4-carboxamide, hydrochloride salt

HRID 497014Notes

Reaction equation

HRID 497014 reaction equation
[Cl:1]C1[CH:7]=[C:6]([C:8]([NH:10][CH2:11][C:12]23[CH2:21][CH:16]4[CH2:17][CH:18]([CH2:20][CH:14]([CH2:15]4)[CH2:13]2)[CH2:19]3)=[O:9])[C:5]([Cl:22])=[CH:4][N:3]=1.C(O[C:28]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)=O)(C)(C)C.Cl>CS(C)=O.CO.O1CCOCC1>[ClH:1].[Cl:22][C:5]1[C:6]([C:8]([NH:10][CH2:11][C:12]23[CH2:13][CH:14]4[CH2:15][CH:16]([CH2:17][CH:18]([CH2:20]4)[CH2:19]2)[CH2:21]3)=[O:9])=[CH:7][C:28]([N:30]2[CH2:31][CH2:32][NH:33][CH2:34][CH2:35]2)=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 11416492N-(1-adamantylmethyl)-2,5-dichloroisonicotinamide

Product 1

HCID 102242375-Chloro-2-piperazinyl-n-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-pyridine-4-carboxamide, hydrochloride saltYield 51.8%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2,5-dichloro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-pyridine-4-carboxamide (0.30 g, Example 1a) and 1-t-butoxycarbonylpiperazine (0.344 g) in dimethylsulfoxide (3 ml) was heated at 160° C. for 40 min. The solution was cooled and partitioned between saturated aqueous sodium bicarbonate solution and dichloromethane and the organic layer dried over magnesium sulphate. Concentration in vacuo and chromatography on silica gave a colourless solid. This was redissolved in methanol and treated with 4M HCl in dioxan (4 ml). Once deprotection was complete the solution was partially concentrated in vacuo then diluted slowly with diethyl ether with rapid stirring. The resulting white precipitate was filtered, washed with diethyl ether and dried to afford the title compound (0.195 g).

Workup

  1. temperatureThe solution was cooled
  2. custompartitioned between saturated aqueous sodium bicarbonate solution and dichloromethane
  3. dry with materialthe organic layer dried over magnesium sulphate
  4. concentrationConcentration in vacuo and chromatography on silica
  5. customgave a colourless solid
  6. concentrationwas partially concentrated in vacuo
  7. additionthen diluted slowly with diethyl ether with rapid stirring
  8. filtrationThe resulting white precipitate was filtered
  9. washwashed with diethyl ether
  10. customdried

Sources & evidence

ORD record
ord-d9337884d7c74167809713ac9b5a1bcd
Source dataset
uspto-grants-2005_09
Patent number
US06949539B2

Reaction notes

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