Sodium Bicarbonate → (S)-4-chloro-1-(1-methoxymethyl-3-methoxypropyl)-6-methyl-1H-1,2,3-triazolo[4,5-c]pyridine

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Reaction Conditions

Reaction Steps

3-amino-2-chloro-6-methyl-4-N-(1-methoxymethyl-3-methoxypropyl)pyridin-4-amine (4.1 g, 14.98 mmol) was dissolved in a mixture of CH2Cl2 (40 mL) and 50% acetic acid (40 mL) and cooled to 0° C. in an ice bath. To that a solution of NaNO2 (1.84 g, 26.86 mmol) in water (10 mL) was added dropwise and the reaction was stirred at 0° C. for 30 min and at 25° C. for 1.5 h. Then the acetic acid was neutralized with solid NaHCO3 and water (80 mL) was added. The mixture was extracted with EtOAc (2×100 mL) and the combined organic extracts were combined and washed with brine (50 mL), dried and stripped in vacuo. The residue was chromatographed on silica gel (40% EtOAc/hexanes eluent) to give the product (4.05 g, 56% overall for the eight steps). NMR(CDCl3)d 7.25 (s, 1H), 5.04-5.13 (m, 1H), 3.98 (dd, 1H, J1=9.9 Hz, J2=8.4 Hz), 3.84 (dd, 1H, J1=10.2 Hz, J2=4.4 Hz), 3.39 (dt, 1H, J1=9.9 Hz, J2=4.8 Hz), 3.25 (s, 3H), 3.17 (s, 3H), 2.91 (dt, 1H, J1=9.5 Hz, J2=4.0 Hz), 2.68 (s, 3H), 2.22-2.6 (m, 2H).

Provenance & Evidence