Hydrochloric Acid → 2-Chloro-5-[[2-(2-hydroxy-ethylamino)-ethylamino]-methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide dihydrochloride

HRID 1816034Notes

Reaction equation

HRID 1816034 reaction equation
[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH:22]=O)=[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].[NH2:24][CH2:25][CH2:26][NH:27][CH2:28][CH2:29][OH:30].[BH4-].[Na+].[ClH:33]>C(O)C.CO.O1CCOCC1.C1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>[ClH:1].[ClH:33].[Cl:1][C:2]1[CH:21]=[CH:20][C:19]([CH2:22][NH:24][CH2:25][CH2:26][NH:27][CH2:28][CH2:29][OH:30])=[CH:18][C:3]=1[C:4]([NH:6][CH2:7][C:8]12[CH2:15][CH:14]3[CH2:13][CH:12]([CH2:11][CH:10]([CH2:16]3)[CH2:9]1)[CH2:17]2)=[O:5]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 8112N-(2-Hydroxyethyl)ethylenediamineHCID 4311764Sodium borohydrideHCID 120853462-Chloro-5-formyl-N-(tricyclo [3.3.1.13,7]dec-1-ylmethyl)-benzamide

Product 1

HCID 98918542-Chloro-5-[[2-(2-hydroxy-ethylamino)-ethylamino]-methyl]-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide dihydrochloride

Reagents, catalysts & solvents 5

HCID 6101p-Toluenesulfonic acidCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-chloro-5-formyl-N-(tricyclo [3.3.1.13,7]dec-1-ylmethyl)-benzamide (0.244 g, Example 1b), 2-(2-aminoethylamino)-ethanol (0.154 g), p-toluenesulfonic acid (0.005 g) and toluene (30 ml) were refluxed together under Dean-Stark conditions for 3hs, cooled and concentrated under reduced pressure to give an oil. This was dissolved in ethanol (30 ml) and cooled to 0 C. under a nitrogen atmosphere. Solid sodium borohydride (0.030 g) was added portionwise to this and the mixture stirred at room temperature for 30 min. The mixture was concentrated under reduced pressure and the residue purified by column chromatography over silica gel (eluting with 7:3:0.3 dichloromethane/methanol/35% aqueous ammonia) to give the free base. This was dissolved in methanol (10 ml) and treated with 4M hydrochloric acid in dioxane (4 ml) to give a solid precipitate. This was filtered off and washed with diethyl ether to afford the title compound as a solid (0.165 g).

Workup

  1. temperaturewere refluxed together under Dean-Stark conditions for 3hs
  2. temperaturecooled
  3. concentrationconcentrated under reduced pressure
  4. customto give an oil
  5. temperaturecooled to 0 C
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customthe residue purified by column chromatography over silica gel (eluting with 7:3:0.3 dichloromethane/methanol/35% aqueous ammonia)
  8. customto give the free base
  9. customto give a solid precipitate
  10. filtrationThis was filtered off
  11. washwashed with diethyl ether

Sources & evidence

ORD record
ord-8b142ba359534e06902693a4de7cbd5d
Source dataset
uspto-grants-2005_04
Patent number
US06881754B2

Reaction notes

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