Nonane → N-(1-Adamantylmethyl)-5-chloro-2-[3-(ethylamino)propyl]isonicotinamide hydrochloride

HRID 1247597Notes

Reaction equation

HRID 1247597 reaction equation
[CH2:1]([NH:4][C:5](=O)OC(C)(C)C)[CH:2]=[CH2:3].[CH3:12]CCCCCCCC.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[C:29]12([CH2:39][NH:40][C:41](=[O:50])[C:42]3[C:47]([Cl:48])=[CH:46][N:45]=[C:44](Br)[CH:43]=3)[CH2:38][CH:33]3[CH2:34][CH:35]([CH2:37][CH:31]([CH2:32]3)[CH2:30]1)[CH2:36]2>O1CCCC1.O.CN(C)C=O.[Cl-].[Na+].O>[ClH:48].[C:29]12([CH2:39][NH:40][C:41](=[O:50])[C:42]3[C:47]([Cl:48])=[CH:46][N:45]=[C:44]([CH2:3][CH2:2][CH2:1][NH:4][CH2:5][CH3:12])[CH:43]=3)[CH2:38][CH:33]3[CH2:34][CH:35]([CH2:37][CH:31]([CH2:32]3)[CH2:30]1)[CH2:36]2

Participants

9

Reactant 4

HCID 8141NonaneHCID 62657Potassium Phosphate, TribasicHCID 4067274tert-butyl N-(prop-2-en-1-yl)carbamateHCID 11773529N-(1-adamantylmethyl)-2-bromo-5-chloroisonicotinamide

Product 1

HCID 21906718N-(1-Adamantylmethyl)-5-chloro-2-[3-(ethylamino)propyl]isonicotinamide hydrochloride

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of tert-butyl allylcarbamate (Example 7(iv)) (0.23 g) in 9-boroabicyclo[3.3.1]nonane (5 ml of a 0.5M solution in tetrahydrofuran) was heated at reflux under nitrogen for 6 hours. The solution was cooled to room temperature and potassium phosphate (1 ml of a 3M solution in water) was added. The mixture was stirred for 15 minutes and a solution of N-(1-adamantylmethyl)-2-bromo-5-chloroisonicotinamide (Example 1(ii)) (0.383 g) and dichloro[1,1′-bis(diphenylphosphino)ferrocenyl]palladium (II) (0.045 g) in anhydrous N,N-dimethylformamide (8 ml) was added. The mixture was stirred for 6 hours, diluted with saturated brine (25 ml) and extracted into ethyl acetate (3×25 ml). The combined extracts were dried over anhydrous sodium sulphate, filtered and concentrated. The residue was purified by chromatography on silica gel eluting with iso-hexane:ethyl acetate (4:1 to 2:1). The isolated material (0.30 g) was dissolved in a solution of hydrogen chloride in 1,4-dioxane (10 ml of a 4M solution) and concentrated; the resultant solid was triturated with ethyl acetate and the solid collected by filtration to afford the titled compound (0.245 g) as a colourless powder.

Workup

  1. temperatureat reflux under nitrogen for 6 hours
  2. stirringThe mixture was stirred for 6 hours
  3. extractionextracted into ethyl acetate (3×25 ml)
  4. dry with materialThe combined extracts were dried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel eluting with iso-hexane:ethyl acetate (4:1 to 2:1)
  8. dissolutionThe isolated material (0.30 g) was dissolved in a solution of hydrogen chloride in 1,4-dioxane (10 ml of a 4M solution) and
  9. concentrationconcentrated
  10. customthe resultant solid was triturated with ethyl acetate
  11. filtrationthe solid collected by filtration

Sources & evidence

ORD record
ord-9c9aa449be4042fea65439079f63ef72
Source dataset
uspto-grants-2006_10
Patent number
US07129246B2

Reaction notes

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