2-Ethynyl-5-methylpyridine → 4-(5-(3,4-dimethoxybenzyl)-1H-1,2,4-triazol-1-yl)-2-methyl-6-((5-methylpyridin-2-yl)ethynyl)pyrimidine

HRID 1498800Notes

Reaction equation

HRID 1498800 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[C:12]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH3:23])[CH:15]=3)=[N:11][CH:10]=[N:9]2)[N:5]=[C:4]([CH3:24])[N:3]=1.[C:25]([C:27]1[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=1)#[CH:26]>C(#N)C.C(N(CC)CC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[CH3:23][O:22][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][C:17]=1[O:20][CH3:21])[CH2:13][C:12]1[N:8]([C:6]2[CH:7]=[C:2]([C:26]#[C:25][C:27]3[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][N:28]=3)[N:3]=[C:4]([CH3:24])[N:5]=2)[N:9]=[CH:10][N:11]=1

Participants

7

Reactant 2

HCID 134006342-Ethynyl-5-methylpyridineHCID 715483344-chloro-6-(5-(3,4-dimethoxybenzyl)-1H-1,2,4-triazol-1-yl)-2-methylpyrimidine

Product 1

HCID 867320644-(5-(3,4-dimethoxybenzyl)-1H-1,2,4-triazol-1-yl)-2-methyl-6-((5-methylpyridin-2-yl)ethynyl)pyrimidine

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
50 °C

Procedure

A slurry of 4-chloro-6-(5-(3,4-dimethoxybenzyl)-1H-1,2,4-triazol-1-yl)-2-methylpyrimidine (1-3, 100 mg, 0.289 mmol, 1.0 eq), 2-ethynyl-5-methylpyridine (67.8 mg, 0.578 mmol, 2.0 eq), bis(triphenylphosphine)palladium(II) dichloride (10.15 mg, 0.014 mmol. 0.050 eq.) and copper(I) iodide (2.203 mg, 0.012 mmol 0.040 eq.) in a mixture of acetonitrile (1 ml) and triethylamine (1 mL) was heated at 50° C. for 16 h. The solvents were removed by roto-evaporation and the resulting residue was purified by silica gel column chromatography (0-100% ethyl acetate in hexanes) to afford 4-(5-(3,4-dimethoxybenzyl)-1H-1,2,4-triazol-1-yl)-2-methyl-6-((5-methylpyridin-2-yl)ethynyl)pyrimidine (1-4). 1H NMR (500 MHz, CDCl3) δ 8.78 (s, 1H), 7.94 (m, 2H), 7.69 (m, 2H), 6.86 (m, 2H), 6.79 (d, 1H, J=8.2 Hz), 4.79 (s, 2H), 3.84 (s, 6H), 2.82 (s, 3H), 2.54 (s, 3H). HRMS m/z (M+H) 429.2029 found, 429.2034 required.

Workup

  1. customThe solvents were removed by roto-evaporation
  2. customthe resulting residue was purified by silica gel column chromatography (0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e5ce1900119348d39b14d664bd1bfe96
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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