Methyl chloroacetate → 2-(Chloromethyl)-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine

HRID 1094033Notes

Reaction equation

CC1C=C(C)C=C(C)C=1S([O-])(=O)=O.[NH2:14][N:15]1[C:20]([CH3:21])=[CH:19][C:18]([CH3:22])=[N:17][C:16]1=[NH2+:23].[OH-].[Na+].CO[C:28](=O)[CH2:29][Cl:30]>CCO>[Cl:30][CH2:29][C:28]1[N:23]=[C:16]2[N:17]=[C:18]([CH3:22])[CH:19]=[C:20]([CH3:21])[N:15]2[N:14]=1

Participants

Conditions

Temperature: 55 °C

Procedure

A mixture of 1-Amino-4,6-dimethyl-1H-pyrimidin-2-ylidene-ammonium 2,4,6-Trimethyl-benzenesulfonate (40 g, 0.1 mol) and NaOH (10 g, 0.2 mol) in 500 mL of EtOH was stirred at 50-60° C. for 1 hour. After chloroacetic acid methyl ester (16.6 g, 0.15 mol) was added, the resultant mixture was stirred at reflux for 4 hours. After being concentrated under reduce pressure, the residue was diluted with water (1000 mL) and extracted with CH2Cl2 (300 mL×3). The combined organic layers were washed with brine (200 mL), dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by column chromatography on silica gel (petroleum ether/EtOAc=2/1) to give 2 g of 2-Chloromethyl-5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidine in 9% yield. 1H NMR (300 MHz, DMSO-d6): δ8.55 (s, 1H), 6.25 (s, 2H), 4.05 (s, 3H), 3.95 (s, 3H); LC-MS (MH+): m/z=196.9, tR (min, method A)=0.52

Workup

temperatureat reflux for 4 hours
concentrationAfter being concentrated
additionthe residue was diluted with water (1000 mL)
extractionextracted with CH2Cl2 (300 mL×3)
washThe combined organic layers were washed with brine (200 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated under vacuum
customThe residue was purified by column chromatography on silica gel (petroleum ether/EtOAc=2/1)

Sources & evidence

ORD record: ord-da4cd447f4814f13bfdf39fa30d37ff3
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08133897B2

Reaction notes

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