Tert-butyl 3-(4-{[(1-adamantylmethyl)amino]-carbonyl}-5-chloropyridin-2-yl)prop-2-ynyl(ethyl)carbamate → N-(1-Adamantylmethyl)-5-chloro-2-[3-(ethylamino)propyl]isonicotinamide hydrochloride

HRID 1247595Notes

Reaction equation

HRID 1247595 reaction equation
[C:1]12([CH2:11][NH:12][C:13]([C:15]3[C:20]([Cl:21])=[CH:19][N:18]=[C:17]([C:22]#[C:23][CH2:24][N:25]([CH2:33][CH3:34])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>[OH-].[Na+]>[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][CH3:34])[CH:16]=3)[CH2:2][CH:3]3[CH2:4][CH:5]([CH2:6][CH:7]([CH2:9]3)[CH2:8]1)[CH2:10]2

Participants

3

Reactant 1

HCID 21906729Tert-butyl 3-(4-{[(1-adamantylmethyl)amino]-carbonyl}-5-chloropyridin-2-yl)prop-2-ynyl(ethyl)carbamate

Product 1

HCID 21906718N-(1-Adamantylmethyl)-5-chloro-2-[3-(ethylamino)propyl]isonicotinamide hydrochlorideYield 19%

Reagents, catalysts & solvents 1

HCID 14798Sodium HydroxideSolvent

Procedure

The titled compound was prepared from tert-butyl 3-(4-{[(1-adamantylmethyl)amino]-carbonyl}-5-chloropyridin-2-yl)prop-2-ynyl(ethyl)carbamate (Example 7(ii)) (0.30 g) by the method of Example 6(ii). The crude hydrochloride salt was suspended in 2M aqueous sodium hydroxide solution (25 ml), extracted into ethyl acetate (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 triturated with ethyl acetate and the solid collected by filtration. Final purification was by preparative reverse phase HPLC to afford the titled compound (0.025 g) as a colourless powder.

Workup

  1. extractionextracted into ethyl acetate (3×25 ml)
  2. concentrationand the combined extracts were concentrated
  3. customThe residue was purified by chromatography on silica gel eluting with dichloromethane
  4. dissolutionThe isolated material was dissolved in a solution of hydrogen chloride in 1,4-dioxane (10 ml of a 4M solution) and
  5. concentrationconcentrated
  6. customthe resultant solid was triturated with ethyl acetate
  7. filtrationthe solid collected by filtration
  8. customFinal purification

Sources & evidence

ORD record
ord-d457e0cd5e604f838065b06d6b6ace58
Source dataset
uspto-grants-2006_10
Patent number
US07129246B2

Reaction notes

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