Ethyl orthoformate → 2-(1H-tetrazol-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine-5-carboxylic acid

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Reaction Steps

Trimethylsilyl trifluoroacetate (1.5 mL, 8.7 mmol) was added to a suspension of 2-amino-6,7-dihydro-5H-cyclopenta[d]pyrimidine-5-carboxylic acid (845 mg, 4.72 mmol) in ethyl acetate (10 mL). A solution was obtained but a precipitate formed within 5 minutes. The reaction mixture was stirred at RT for 5 minutes and triethyl orthoformate (1.4 mL, 8.4 mmol) was added. The mixture was stirred at RT for 5 minutes and azidotrimethylsilane (1.1 mL, 8.4 mmol) was added. The resulting suspension was stirred at RT overnight. The solvent was evaporated. The residue was purified by chromatography on silica gel (80 g cartridge) using CH2Cl2 (A) and CH2Cl2:MeOH:AcOH 90:10:1 (B) with gradient elution (100% A to 100% B over 16 column volumes) to afford crude product which was further purified by preparative HPLC to afford the title compound: NMR 500 MHz (CD3OD) 10.00 (s, 1H); 8.88 (s, 1H); 4.32 (t, 1H); 3.11-3.15 (m, 2H); 2.47-2.63 (m, 2H); LC/MS (M+Na)+ at 255, (M+1)+ at 233, (M+1-N2)+ at 205.

Provenance & Evidence