Dimethylacetamide → HCID 68616370, compound

A 22 ml Supelco vial under Argon is loaded with 0.231 mmol of tris(dibenzylidene-acetone)dipalladium(0) (Pd2(dba)3) and 0.463 mmol of 1,1′-bis(diphenyl-phosphino)ferrocene (dppf). 5 ml of dry N,N-dimethyl acetamide is added and the dark solution is stirred at room temperature for 10 minutes. 1.388 mmol of zinc cyanide, and then a solution of 2.313 mmol of 6-chloro-6′,7′-dihydro-3H,5′H-spiro[2-benzofuran-1,8′-imidazo[1,5-a]pyridine] in 2.5 ml of dry N,N-dimethyl acetamide are successively added. The reaction mixture is briefly degassed, put under an atmosphere of Argon then directly placed in an oil bath pre-heated to 80° C. The dark brown mixture is then stirred for 15 hours at 140° C. If the conversion is not complete (HPLC check), a fresh solution of Pd2(dba)3 and dppf in N,N-dimethyl acetamide, previously stirred at room temperature for 10 minutes, is added and the stirring is continued at 140° C. till no more starting material is detected. The reaction mixture is cooled to room temperature and evaporated to dryness. The residue is diluted with 30 ml of dichloromethane and 100 ml of tert-butyl-methyl ether and washed with aqueous HCl 2N (2×50 ml). The combined aqueous phases are basified with 75 ml of 4N aqueous NaOH and extracted with dichloromethane (3×200 ml). The combined organic phases are dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue is purified by flash chromatography (SiO2 60 F) to afford the title compound as a beige solid. Rf=0.13 (EtOAc-methanol 10:1); Rt=2.59 (gradient I).

1. customThe reaction mixture is briefly degassed
2. customthen directly placed in an oil bath
3. temperaturepre-heated to 80° C
4. stirringThe dark brown mixture is then stirred for 15 hours at 140° C
5. stirringa fresh solution of Pd2(dba)3 and dppf in N,N-dimethyl acetamide, previously stirred at room temperature for 10 minutes
6. additionis added
7. customis continued at 140° C.
8. temperatureThe reaction mixture is cooled to room temperature
9. customevaporated to dryness
10. additionThe residue is diluted with 30 ml of dichloromethane and 100 ml of tert-butyl-methyl ether
11. washwashed with aqueous HCl 2N (2×50 ml)
12. extractionextracted with dichloromethane (3×200 ml)
13. dry with materialThe combined organic phases are dried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe resulting residue is purified by flash chromatography (SiO2 60 F)

ORD record

ord-57700f6b0f8a477db83a84a23772e753

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08324235B2