Methanol → Pyrrolo[1,2-a]pyrimidine

A mixture of methyl 5-nitro-4-quinolin-4-yl-1H-pyrrole-2-carboxylate (23, 90 mg, 0.3 mmol), Pd/C (5%, 45 mg), and MeOH (15 mL) was stirred under argon for 5 min, then under hydrogen for 40 min before removal of the catalyst by filtration through celite. To the orange color filtrate was added 2-(4-methoxyphenyl)malondialdehyde (54 mg, 0.3 mmol) followed by AcOH (2 mL). The resulting reaction mixture was stirred overnight at 82° C., then cooled to rt, quenched with sat. NaHCO3, and extracted with ethyl acetate and CH2Cl2. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel using CH2Cl2/MeOH (90:10) to give 25 as a yellow solid (90 mg, 73%). 1H NMR (DMSO-d6, 500 MHz) δ 9.80 (d, J=3.0 Hz, 1H), 8.97 (d, J=5.0 Hz, 1H), 8.87 (d, J=3.0 Hz, 1H), 8.10 (m, 1H), 8.04 (s, 1H), 7.80 (m, 1H), 7.75 (d, J=5.0 Hz, 1H), 7.75 (d, J=8.5 Hz, 2H), 7.61 (m, 1H), 7.15 (d, J=8.5 Hz, 2H), 3.94 (s, 3H), 3.84 (s, 3H); mp 230-231° C.

1. customunder hydrogen for 40 min before removal of the catalyst
2. filtrationby filtration through celite
3. customThe resulting reaction mixture
4. stirringwas stirred overnight at 82° C.
5. customquenched with sat. NaHCO3
6. extractionextracted with ethyl acetate and CH2Cl2
7. dry with materialThe combined organic layers were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by column chromatography on silica gel

ORD record

ord-9ab33185365d420fb123d0ca92f3fafc

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507501B2