N-(1-adamantylmethyl)-2-bromo-5-chloroisonicotinamide → tert-Butyl 3-(4-{[(1-adamantylmethyl)amino]carbonyl}-5-chloropyridin-2-yl)prop-2-ynyl[3-(tetrahydro-2H-pyran-2-yloxy)propyl]carbamate

HRID 1247583Notes

Reaction equation

HRID 1247583 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]([N:26]([CH2:34][CH2:35][CH2:36][O:37][CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][O:39]1)[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:24]#[CH:25]>C(#N)C.C(N(CC)CC)C>[C:1]12([CH2:11][NH:12][C:13]([C:14]3[C:19]([Cl:20])=[CH:18][N:17]=[C:16]([C:25]#[C:24][CH2:23][N:26]([CH2:34][CH2:35][CH2:36][O:37][CH:38]4[CH2:43][CH2:42][CH2:41][CH2:40][O:39]4)[C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:30])[CH3:31])[CH:15]=3)=[O:22])[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 11773529N-(1-adamantylmethyl)-2-bromo-5-chloroisonicotinamideHCID 86595925tert-Butyl prop-2-ynyl[3-(tetrahydro-2H-pyran-2-yloxy)propyl]carbamate

Product 1

HCID 69539581tert-Butyl 3-(4-{[(1-adamantylmethyl)amino]carbonyl}-5-chloropyridin-2-yl)prop-2-ynyl[3-(tetrahydro-2H-pyran-2-yloxy)propyl]carbamateYield 58%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

A suspension of N-(1-adamantylmethyl)-2-bromo-5-chloroisonicotinamide (Example 2(i)) (0.43 g) and tert-butyl prop-2-ynyl[3-(tetrahydro-2H-pyran-2-yloxy)propyl]carbamate (Example 2(ii)) (0.60 g) in anhydrous acetonitrile (6 ml) and triethylamine (6 ml) was purged with nitrogen for 5 minutes and then copper (I) iodide (0.004 g) and bis-triphenyphosphine palladium dichloride (0.014 g) were added. The mixture was stirred under nitrogen for 2 hours. The mixture was concentrated and the residue was purified by chromatography on silica gel eluting with iso-hexane:ethyl acetate (19:1 to 7:3) to afford the sub-titled compound (0.39 g) as a yellow gum.

Workup

  1. customwas purged with nitrogen for 5 minutes
  2. additioncopper (I) iodide (0.004 g) and bis-triphenyphosphine palladium dichloride (0.014 g) were added
  3. concentrationThe mixture was concentrated
  4. customthe residue was purified by chromatography on silica gel eluting with iso-hexane:ethyl acetate (19:1 to 7:3)

Sources & evidence

ORD record
ord-eed5aed0ee9a4b8b8903bfaa9b2b1cb5
Source dataset
uspto-grants-2006_10
Patent number
US07129246B2

Reaction notes

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