Hydrochloric Acid → 2-Chloro-5-[[4-[(2-hydroxyethyl)amino]-1-piperidinyl]methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide, hydrochloride salt

HRID 2298111Notes

Reaction equation

HRID 2298111 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH2:22][N:23]2[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]2)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:17][CH:12]3[CH2:13][CH:14]([CH2:16][CH:10]([CH2:11]3)[CH2:9]1)[CH2:15]2)=[O:5].[CH2:30]([CH2:32][NH2:33])[OH:31].C([BH3-])#N.[Na+].Cl>CO.O1CCOCC1.CCOCC.CO>[ClH:1].[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([NH:33][CH2:32][CH2:30][OH:31])[CH2:25][CH2:24]2)=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:9][CH:10]3[CH2:11][CH:12]([CH2:13][CH:14]([CH2:16]3)[CH2:15]1)[CH2:17]2)=[O:5]

Participants

8

Reactant 4

HCID 313Hydrochloric Acid3×HCID 700EthanolamineHCID 5003444Sodium cyanoborohydrideHCID 183815232-Chloro-5-[(4-oxo-1-piperidinyl)methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide

Product 1

HCID 183814882-Chloro-5-[[4-[(2-hydroxyethyl)amino]-1-piperidinyl]methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide, hydrochloride salt

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent2×HCID 21864698Diethyl ether methanolSolvent

Procedure

To a solution of 2-chloro-5-[(4-oxo-1-piperidinyl)methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.150 g, Example 83a) in methanol (3ml ) at room temperature were added ethanolamine (0.11 ml) and sodium cyanoborohydride (0.068g). The pH was adjusted to 6 by adding a 4N solution of hydrogen chloride in dioxane and the reaction stirred for 48 h. The reaction was acidified with concentrated hydrochloric acid until gas evolution ceased. The precipitate was removed by filtration and the filtrate concentrated under vacuum. The residue was partitioned between ethyl acetate and water. The aqueous layer was basified with 5% aqueous sodium hydroxide and extracted with dichloromethane. The organics were washed with brine and dried over magnesium sulfate. The crude material was purified on silica gel (5% 7N ammonia in methanol/95% dichloromethane) to afford a white foam which was dissolved in ether/methanol and treated with a 4N solution of hydrogen chloride in dioxane to give the title compound (0.135 g).

Workup

  1. customThe precipitate was removed by filtration
  2. concentrationthe filtrate concentrated under vacuum
  3. customThe residue was partitioned between ethyl acetate and water
  4. extractionextracted with dichloromethane
  5. washThe organics were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. customThe crude material was purified on silica gel (5% 7N ammonia in methanol/95% dichloromethane)
  8. customto afford a white foam which

Sources & evidence

ORD record
ord-d11ea039404a4ecbbbe2ee1ec8060f06
Source dataset
uspto-grants-2002_12
Patent number
US06492355B1

Reaction notes

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