Sodium hydride → HCID 59341794, Verbindung

To a solution of tert-butyl {(3R)-1-[1-(quinolin-6-ylmethyl)-1H-[1,2,3]triazolo[4,5-b]pyrazin-6-yl]pyrrolidin-3-yl}carbamate (300 mg, 0.672 mmol) in anhydrous DMF (2.0 ml) was added 95% NaH (25.4 mg, 1.01 mmol). After stirring at R.T. for 10 mins, to the reaction mixture was added iodoethanol (288.9 mg, 1.68 mmol). After stirring at 70° C. for 16 h, to the reaction mixture was added iodoethanol (288.9 mg, 1.68 mmol). After stirring at 90° C. for 7 h, 105° C. for 32 h, the reaction mixture was quenched with water and filtered. The eluent was extracted with 2:1 EtOAc:toluene (2×30 ml). The organic layer was dried with K2CO3, filtered and concentrated. The resulting residue was dissolved in CH2Cl2 (10 ml) and TFA (0.5 ml) and MeOH (1 pipet drop) were added. After stirring at R.T for 16 h, the reaction mixture was concentrated. The resulting residue was purified via reversed phase column eluted with 0.1% TFA CAN: water to give the desired product (1.6 mg).

1. stirringAfter stirring at 70° C. for 16 h, to the reaction mixture
2. stirringAfter stirring at 90° C. for 7 h, 105° C. for 32 h
3. customthe reaction mixture was quenched with water
4. filtrationfiltered
5. extractionThe eluent was extracted with 2:1 EtOAc
6. dry with materialThe organic layer was dried with K2CO3
7. filtrationfiltered
8. concentrationconcentrated
9. dissolutionThe resulting residue was dissolved in CH2Cl2 (10 ml)
10. additionTFA (0.5 ml) and MeOH (1 pipet drop) were added
11. stirringAfter stirring at R.T for 16 h
12. concentrationthe reaction mixture was concentrated
13. customThe resulting residue was purified via reversed phase column
14. washeluted with 0.1% TFA CAN

ORD-Eintrag

ord-c6f2b30405dc4efca0b99cb12c36ac12

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07732604B2