tert-Butyl 3-(4-{[(1-adamantylmethyl)amino]carbonyl}-5-chloropyridin-2-yl)propyl[3-(tetrahydro-2H-pyran-2-yloxy)propyl]carbamate → N-(1-Adamantylmethyl)-5-chloro-2-{3-[(3-hydroxypropyl)amino]propyl}isonicotinamide dihydrochloride

HRID 1247585Notes

Reaction equation

HRID 1247585 reaction equation
[C:1]12([CH2:11][NH:12][C:13]([C:15]3[C:20]([Cl:21])=[CH:19][N:18]=[C:17]([CH2:22][CH2:23][CH2:24][N:25]([CH2:33][CH2:34][CH2:35][O:36]C4CCCCO4)C(=O)OC(C)(C)C)[CH:16]=3)=[O:14])[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2>CO.Cl>[ClH:21].[ClH:21].[C:1]12([CH2:11][NH:12][C:13](=[O:14])[C:15]3[C:20]([Cl:21])=[CH:19][N:18]=[C:17]([CH2:22][CH2:23][CH2:24][NH:25][CH2:33][CH2:34][CH2:35][OH:36])[CH:16]=3)[CH2:8][CH:7]3[CH2:9][CH:3]([CH2:4][CH:5]([CH2:6]3)[CH2:10]1)[CH2:2]2

Participants

4

Reactant 1

HCID 86595926tert-Butyl 3-(4-{[(1-adamantylmethyl)amino]carbonyl}-5-chloropyridin-2-yl)propyl[3-(tetrahydro-2H-pyran-2-yloxy)propyl]carbamate

Product 1

HCID 21906713N-(1-Adamantylmethyl)-5-chloro-2-{3-[(3-hydroxypropyl)amino]propyl}isonicotinamide dihydrochlorideYield 176.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

tert-Butyl 3-(4-{[(1-adamantylmethyl)amino]carbonyl}-5-chloropyridin-2-yl)propyl[3-(tetrahydro-2H-pyran-2-yloxy)propyl]carbamate (Example 2(iv)) (0.24 g) was dissolved in a mixture of methanol (10 ml) and 2M aqueous hydrochloric acid solution (10 ml); the solution was left to stand for 0.5 hours. The mixture was concentrated and the residue diluted with 2M aqueous sodium hydroxide solution (25 ml). The mixture was extracted into dichloromethane (3×25 ml) and the combined extracts were concentrated. The residue was dissolved in a solution of hydrogen chloride in 1,4-dioxane (10 ml of a 4M solution) and left to stand for 0.5 hours. The solution was concentrated and the residue suspended in 2M aqueous sodium hydroxide solution (25 ml), extracted into dichloromethane (3×25 ml) and the combined extracts were concentrated. The residue was purified by chromatography on silica gel eluting with dichloromethane:methanol:0.88 aqueous ammonia (89:10:1). The isolated material was dissolved in a solution of hydrogen chloride in 1,4-dioxane (10 ml of a 4M solution) and concentrated; the resultant solid was recrystallised from ethyl acetate/methanol to afford the titled compound (0.115 g) as a colourless solid.

Workup

  1. waitthe solution was left
  2. concentrationThe mixture was concentrated
  3. additionthe residue diluted with 2M aqueous sodium hydroxide solution (25 ml)
  4. extractionThe mixture was extracted into dichloromethane (3×25 ml)
  5. concentrationthe combined extracts were concentrated
  6. dissolutionThe residue was dissolved in a solution of hydrogen chloride in 1,4-dioxane (10 ml of a 4M solution) and
  7. waitleft
  8. waitto stand for 0.5 hours
  9. concentrationThe solution was concentrated
  10. extractionextracted into dichloromethane (3×25 ml)
  11. concentrationthe combined extracts were concentrated
  12. customThe residue was purified by chromatography on silica gel eluting with dichloromethane
  13. dissolutionThe isolated material was dissolved in a solution of hydrogen chloride in 1,4-dioxane (10 ml of a 4M solution) and
  14. concentrationconcentrated
  15. customthe resultant solid was recrystallised from ethyl acetate/methanol

Sources & evidence

ORD record
ord-a11e0c794dc8463e97b91c8f732f15ae
Source dataset
uspto-grants-2006_10
Patent number
US07129246B2

Reaction notes

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