Methyl chloroacetate → 2-(Chloromethyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine

To a solution of 3,6-Dimethyl-2-pyridinamine (2.00 g, 16.4 mmol) in 50 mL of DCM was added dropwise a solution of hydroxylamine-2,4,6-Trimethyl-benzenesulfonate (4.22 g, 19.6 mmol) in 50 mL of CH2Cl2 at 0° C., and the mixture was stirred and allowed to warm to room temperature. The solvents were evaporated and the residue dissolved in 80 mL of MeOH then treated with DBU (3.43 mL, 22.9 mmol) and the solution stirred for 5 mins. After chloroacetic acid methyl ester (1.44 mL, 16.4 mmol) was added, the resultant mixture was stirred at room temperature for 48 h. After being concentrated under reduce pressure, the residue was diluted with water (100 mL) and extracted with EtOAc (3×100 mL). The combined organic layers were washed with water (50 mL), brine (50 mL), dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc=2/1) to give 2.65 g of 2-Chloromethyl-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridine in 82% yield. LC-MS (MH+): m/z=195.9, tR (minutes)=1.14

1. customThe solvents were evaporated
2. dissolutionthe residue dissolved in 80 mL of MeOH
3. stirringthe solution stirred for 5 mins
4. concentrationAfter being concentrated
5. additionthe residue was diluted with water (100 mL)
6. extractionextracted with EtOAc (3×100 mL)
7. washThe combined organic layers were washed with water (50 mL), brine (50 mL)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under vacuum
11. customThe residue was purified by column chromatography on silica gel (petroleum ether/EtOAc=2/1)

ORD-Eintrag

ord-57e8629e4fb640c2b58ad5c440a8af8b

Quelldatensatz

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08796304B2