Diisopropylethylamine → N-{4-[5-bromo-4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-furyl]-5-methylpyridin-2-yl}acetamide

HRID 537066Notes

Reaction equation

HRID 537066 reaction equation
[Br:1][C:2]1[O:6][C:5]([C:7]2[C:12]([CH3:13])=[CH:11][N:10]=[C:9]([NH:14][C:15](=[O:17])[CH3:16])[CH:8]=2)=[CH:4][C:3]=1[C:18]1[N:22]=[CH:21][NH:20][N:19]=1.CCN(C(C)C)C(C)C.[CH3:32][Si:33]([CH2:36][CH2:37][O:38][CH2:39]Cl)([CH3:35])[CH3:34]>CN(C=O)C.O>[Br:1][C:2]1[O:6][C:5]([C:7]2[C:12]([CH3:13])=[CH:11][N:10]=[C:9]([NH:14][C:15](=[O:17])[CH3:16])[CH:8]=2)=[CH:4][C:3]=1[C:18]1[N:22]=[CH:21][N:20]([CH2:39][O:38][CH2:37][CH2:36][Si:33]([CH3:35])([CH3:34])[CH3:32])[N:19]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178474032HCID 178474032, compound

Product 1

HCID 66749395N-{4-[5-bromo-4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-furyl]-5-methylpyridin-2-yl}acetamideYield 21%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N-{4-[5-bromo-4-(1H-1,2,4-triazol-3-yl)-2-furyl]-5-methylpyridin-2-yl}acetamide (6.0 g, 16.6 mmol) in dry DMF (150 mL) was allowed to stir at 0° C. To this cooled solution was added DIEA (6.5 g, 5.0 mmol) portionwise over 20 min under an atmosphere of nitrogen. The reaction mixture was allowed to stir for 10 min at 0° C. and then SEM-Cl (5.5 g, 33.2 mmol) in dry DMF was add dropwise over 10 min. The reaction mixture was allowed to stir at 0° C. for 10 min and then allowed to warm to rt and allowed to stir for 3 h. The reaction mixture was diluted with water and extracted with EtOAc. The organic solutions were combined, washed with water and brine, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography to give N-{4-[5-bromo-4-(1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,2,4-triazol-3-yl)-2-furyl]-5-methylpyridin-2-yl}acetamide (1.1 g, 21%) plus an additional SEM regioisomer (1.7 g, 25%).

Workup

  1. stirringto stir for 10 min at 0° C.
  2. stirringto stir at 0° C. for 10 min
  3. temperatureto warm to rt
  4. stirringto stir for 3 h
  5. extractionextracted with EtOAc
  6. washwashed with water and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-2f5b6f7adf9e4ea49543e5e975f6c994
Source dataset
uspto-grants-2014_10
Patent number
US08859768B2

Reaction notes

Loading…