Sodium Hydroxide → (2,6-difluorophenyl)-N-[5-(7-methyl-2H,3H-benzo[e]1,4-dioxin-6-yl)pyrazin-2-yl]carboxamide

To a solution of 184 (25 mg, 0.1 mmol) in CH2Cl2 was added 4-dimethylaminopyridine (DMAP, 1.2 mg, 0.01 mmol), 2,6-difluorobenzol chloride (53 mg, 0.3 mmol) and diisopropylethylamine (DIEA, 62 mg, 0.48 mmol). The reaction mixture was stirred for 2 h at room temperature. The reaction was quenched with saturated NaHCO3 (20 ml) and extracted with EtOAc. The organic solvent was removed in vacuo. The residue was dissolved in THF:MeOH (1:1) and added 1N NaOH (2 eq). The mixture was stirred for 10 min at ambient temperature. The reaction solution was concentrated in vacuo and residue was extracted with EtOAc. The crude product was purified by ISCO column and HPLC. Fractions containing pure product were combined and evaporated. The white solid 194 (3.3 mg, 9%) was obtained. LC-MS: calcd. for C20H15F2N3O3: 384 (M+1).

1. customThe reaction was quenched with saturated NaHCO3 (20 ml)
2. extractionextracted with EtOAc
3. customThe organic solvent was removed in vacuo
4. dissolutionThe residue was dissolved in THF:MeOH (1:1)
5. stirringThe mixture was stirred for 10 min at ambient temperature
6. concentrationThe reaction solution was concentrated in vacuo and residue
7. extractionwas extracted with EtOAc
8. customThe crude product was purified by ISCO column and HPLC
9. additionFractions containing pure product
10. customevaporated

ORD record

ord-6c559d00b69f4fa98ceb0dfd2a9eea16

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08980629B2