Propargyl alcohol → N-(1-Adamantylmethyl)-5-chloro-2-(3-hydroxy-1-propynyl)isonicotinamide

HRID 1247579Notes

Reaction equation

HRID 1247579 reaction equation
[C:1]12([CH2:11][NH:12][C:13](=[O:22])[C:14]3[C:19]([Cl:20])=[CH:18][N:17]=[C:16](Br)[CH:15]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[CH2:23]([OH:26])[C:24]#[CH:25]>[Cu]I.C(NCC)C>[C:1]12([CH2:11][NH:12][C:13](=[O:22])[C:14]3[C:19]([Cl:20])=[CH:18][N:17]=[C:16]([C:25]#[C:24][CH2:23][OH:26])[CH:15]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2

Participants

5

Reactant 2

HCID 7859Propargyl alcoholHCID 11773529N-(1-adamantylmethyl)-2-bromo-5-chloroisonicotinamide

Product 1

HCID 21906723N-(1-Adamantylmethyl)-5-chloro-2-(3-hydroxy-1-propynyl)isonicotinamideYield 53.5%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8021DiethylamineSolvent

Procedure

A mixture of N-(1-adamantylmethyl)-2-bromo-5-chloroisonicotinamide (Example 1(ii)) (0.96 g), propargyl alcohol (0.16 g), copper (I) iodide, bis-triphenylphosphine palladium is dichloride (0.035 g) and diethylamine (10 ml) was stirred together at room temperature for 20 hours. The mixture was concentrated and the residue partitioned between ethyl acetate and 1M aqueous hydrochloric acid solution (2×25 ml) and the mixture was extracted into ethyl acetate (3×25 ml). The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by chromatography on silica gel eluting with ethyl acetate:iso-hexane (1:4 to 1:1) and then ethyl acetate to afford the sub-titled compound (0.48 g) as an oil.

Workup

  1. concentrationThe mixture was concentrated
  2. customthe residue partitioned between ethyl acetate and 1M aqueous hydrochloric acid solution (2×25 ml)
  3. extractionthe mixture was extracted into ethyl acetate (3×25 ml)
  4. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel eluting with ethyl acetate:iso-hexane (1:4 to 1:1)

Sources & evidence

ORD record
ord-ca47c98aa6d046849e2f7a0a43917eeb
Source dataset
uspto-grants-2006_10
Patent number
US07129246B2

Reaction notes

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