Dimethylformamide → HCID 22135433, compound

To an ice-cooled solution of 0.32 mL (4.1 mmol) of dimethylformamide in 3 mL of dichloromethane was added dropwise 0.4 mL (4.1 mmol) of phosphorus oxychloride. The reaction mixture was stirred at room temperature for 15 minutes and a solution of 680 mg (2.7 mmol) of 3-(3-morpholin-4-yl-propyl)-4,5,6,7-tetrahydro-1H-indole in 20 mL of dichloromethane was added dropwise at 0° C. The mixture was refluxed at 60° C. for 4 hours and cooled in an ice bath. Ice cubes were slowly added to the mixture followed by addition of 2 N sodium hydroxide to pH 12. The mixture was stirred at room temperature for 30 minutes and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated to give crude product which was purified on a silica gel column eluting with dichloromethane-methanol-ammonium hydroxide (98:2:1) to give 600 mg (83% yield) of 3-(3-morpholin-4-yl-propyl)-4,5,6,7-tetrahydro-1H-indole-2-carbaldehyde as a dark red oil. 1H-NMR (360 MHz, dimethylsulfoxide-d6) δ 11.33 (s, br, 1H, NH). MS m/z 277 [M+1].

1. temperatureThe mixture was refluxed at 60° C. for 4 hours
2. temperaturecooled in an ice bath
3. additionIce cubes were slowly added to the mixture
4. stirringThe mixture was stirred at room temperature for 30 minutes
5. extractionextracted with ethyl acetate
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. concentrationconcentrated
9. customto give crude product which
10. customwas purified on a silica gel column
11. washeluting with dichloromethane-methanol-ammonium hydroxide (98:2:1)

ORD record

ord-1acb4603f4ea4abb9897441f4aef3480

Source dataset

uspto-grants-2007_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07157577B2