Acetic Acid → HCID 178521694, compound

Participants

Reaction Conditions

Reaction Steps

To a medium size microwave vial was added 5 mL of acetic acid and 850 mgs of the crude reaction mixture prepared in the previous step (benzyl 1-(4-aminopyridin-3-lcarbamoyl)cyclopropylcarbamate and benzyl 1-(3-aminopyridin-4-ylcarbamoyl)cyclopropylcarbamate). The vial was sealed and the mixture heated at 120° C. for 70 minutes in the microwave. The vessel was cooled to near 0° C. and 50 mL of cold saturated sodium carbonate was added along with 100 mL of 10:1 DCM/methanol. The product was extracted; the organics washed with brine, dried over magnesium sulfate and evaporated. The product mixture was taken up in 15 mL of methanol and purified using a Shimadzu preparative HPLC employing methanol/water/trifluoroacetic acid where solvent A was 10% methanol/90% water/0.1% trifluoroacetic acid and solvent B was 10% water/90% methanol/0.1% trifluoroacetic acid with a Phenomenex-Luna 10 μm C18 30×100 mm column at a gradient of 0-100% B and a flow rate of 40 mL/min. over 15 minutes with a 10 minute hold. Solvent was removed giving a 70% yield of benzyl 1-(1H-imidazo[4,5-c]pyridin-2-yl)cyclopropylcarbamate as a light yellow solid. 1H NMR (400 MHz, CD3OD) δ ppm 1.44-1.59 (m, 2 H), 1.68-1.83 (m, 2 H), 5.05-5.14 (m, 2 H), 6.99-7.14 (m, 1 H), 7.19-7.41 (m, 4 H), 7.88-7.97 (m, 1 H), 8.40 (d, J=6.5 Hz, 1 H), 8.97 (s, 1H). LCMS rt=1.483 min., m/z 309.2 (M+H), 94.5% purity.

Provenance & Evidence