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

HRID 1498801Notes

Reaction equation

HRID 1498801 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[CH2:6][C:7]1[N:11]([C:12]2[CH:17]=[C:16]([C:18]#[C:19][C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=3)[N:15]=[C:14]([CH3:27])[N:13]=2)[N:10]=[CH:9][N:8]=1>ClCCl.C(O)C.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:28]=[CH:29][C:30]=1[O:31][CH3:32])[CH2:6][C:7]1[N:11]([C:12]2[CH:17]=[C:16]([CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][N:21]=3)[N:15]=[C:14]([CH3:27])[N:13]=2)[N:10]=[CH:9][N:8]=1

Participants

5

Reactant 1

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

Product 1

HCID 867320654-(5-(3,4-dimethoxybenzyl)-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(5-methylpyridin-2-yl)ethyl)pyrimidine

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A slurry of 4-(5-(3,4-dimethoxybenzyl)-1H-1,2,4-triazol-1-yl)-2-methyl-6-((5-methylpyridin-2-yl)ethynyl)pyrimidine (1-4, 80 mg, 0.188 mmol, 1.0 eq.) in a mixture of dichloromethane (3 ml) and ethanol (3 ml) was treated with palladium on carbon (60 mg, 0.564 mmol, 3.0 eq.) under a hydrogen balloon for 4 hours. The reaction mixture was filtered through C-lite, and the C-lite was washed with dichloromethane (3×100 mL). The filtrate was concentrated and purified by reverse phase liquid chromatography (H2OCH3CN gradient w/ 0.1% TFA present) to afford 4-(5-(3,4-dimethoxybenzyl)-1H-1,2,4-triazol-1-yl)-2-methyl-6-(2-(5-methylpyridin-2-yl)ethyl)pyrimidine (1-5). 1H NMR (500 MHz, CDCl3) δ 8.36 (s, 1H), 7.95 (s, 1H), 7.57 (s, 1H), 7.38 (dd, 1H, J=7.9 Hz, 2.3 Hz), 7.04 (d, 1H, J=7.9 Hz), 6.86 (m, 2H), 6.79 (d, 1H, J=8.1 Hz), 4.75 (s, 2H), 3.84 (s, 3H), 3.83 (s, 3H), 3.22 (s, 4H), 2.75 (s, 3H), 2.69 (s, 3H), 2.30 (s, 3H) HRMS m/z (M+H) 431.2185 found, 431.2190 required.

Workup

  1. filtrationThe reaction mixture was filtered through C-lite
  2. washthe C-lite was washed with dichloromethane (3×100 mL)
  3. concentrationThe filtrate was concentrated
  4. custompurified by reverse phase liquid chromatography (H2OCH3CN gradient w/ 0.1% TFA present)

Sources & evidence

ORD record
ord-f2f34aea13ac4c3eaa4b01a6b72042be
Source dataset
uspto-grants-2015_12
Patent number
US09200001B2

Reaction notes

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