Sodium ethoxide → 2'-(3-(4-(4-chlorophenyl)piperazin-1-yl)propyl)-7',8'-dihydro-3'H-spiro[cyclopropane-1,6'-quinazolin]-4'(5'H)-one

Sodium (0.094 g, 4.08 mmol) was added to ethanol (15 ml) under stirring condition at room temperature. The resulting mixture was stirred for 30 min. To this freshly prepared clear solution of sodium ethoxide, were added ethyl 6-oxospiro[2.5]octane-5-carboxylate (0.4 g, 2.03 mmol) and 4-(4-(4-chlorophenyl) piperazin-1-yl)butanimidamide (0.343 g, 1.223 mmol) and the reaction mixture was heated at 85° C. for 18 h. The progress of the reaction was monitored by TLC. The reaction mixture was cooled to room temperature and concentrated under reduced pressure to obtain crude residue which was dissolved with water (15 ml). Aqueous layer was extracted with ethylacetate (2×30 ml). The combined organic layer was dried over sodium sulphate, filtered and solvent was removed under reduced pressure to obtain a crude product which was purified by flash chromatography over silica gel (100-200 mesh) using 3-4% methanol in dichloromethane as eluent to obtain title compound (0.030 g, 4% yield).

1. stirringThe resulting mixture was stirred for 30 min
2. temperaturethe reaction mixture was heated at 85° C. for 18 h
3. temperatureThe reaction mixture was cooled to room temperature
4. concentrationconcentrated under reduced pressure
5. customto obtain crude residue which
6. extractionAqueous layer was extracted with ethylacetate (2×30 ml)
7. dry with materialThe combined organic layer was dried over sodium sulphate
8. filtrationfiltered
9. customsolvent was removed under reduced pressure
10. customto obtain a crude product which
11. customwas purified by flash chromatography over silica gel (100-200 mesh)

ORDレコード

ord-fdcd9f8d0e0740e8a9bd794db78ffaa3

出典データセット

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09359367B2