Hydrochloric Acid → 5-Chloro-2-(4-piperidinyloxy)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-pyridine4-carboxamide, hydrochloride salt

HRID 497016Notes

Reaction equation

HRID 497016 reaction equation
[Cl:1][C:2]1[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(OC([N:30]1[CH2:35][CH2:34][CH:33]([OH:36])[CH2:32][CH2:31]1)=O)(C)(C)C.[H-].[Na+].Cl>O1CCCC1.CO.O1CCOCC1.C(O)(=O)C>[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:2]([O:36][CH:33]2[CH2:34][CH2:35][NH:30][CH2:31][CH2:32]2)=[N:3][CH:4]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 11416492N-(1-adamantylmethyl)-2,5-dichloroisonicotinamide

Product 1

HCID 101817285-Chloro-2-(4-piperidinyloxy)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-pyridine4-carboxamide, hydrochloride saltYield 23.1%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 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-butoxycarbonylpiperidine-4-ol (0.344 g) in anhydrous tetrahydrofuran (10 ml) was heated with sodium hydride (50 mg, 60% dispersion) at 70° C. for 24 hours. The solution was cooled, glacial acetic acid (0.1 ml) was added and the mixture partitioned between saturated aqueous sodium bicarbonate solution and dichloromethane. The organic layer was dried over magnesium sulphate, concentrated in vacuo and chromatographed on silica (ethyl acetate: isohexane) to give a colourless solid. This was redissolved in methanol (20 ml) and treated with 4M HCl in dioxan (4 ml). Once deprotection was complete (14 hours) 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 (0.090 g).

Workup

  1. temperatureThe solution was cooled
  2. customthe mixture partitioned between saturated aqueous sodium bicarbonate solution and dichloromethane
  3. dry with materialThe organic layer was dried over magnesium sulphate
  4. concentrationconcentrated in vacuo
  5. customchromatographed on silica (ethyl acetate: isohexane)
  6. customto give a colourless solid
  7. custom(14 hours)
  8. concentrationwas partially concentrated in vacuo
  9. additionthen diluted slowly with diethyl ether with rapid stirring
  10. filtrationThe resulting white precipitate was filtered
  11. washwashed with diethyl ether
  12. customdried

Sources & evidence

ORD record
ord-fdd6d493594a41eb92e8cea4046934f4
Source dataset
uspto-grants-2005_09
Patent number
US06949539B2

Reaction notes

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