Sodium bis(trimethylsilyl)amide → HCID 10161354, compound

Temperature

0 °C

3,5-dichloro-1-[(1R)-1-cyclopropylpropyl]-2(1H)-pyrazinone (67.9 mg, 0.275 mmol) and 5-bromo-7-methoxy-3,4-dihydro-2H-1,4-benzoxazine (67 mg, 0.275 mmol) were combined in THF (1.4 mL). The mixture was cooled to 0° C. and was treated with NaHMDS (302 μL, 0.302 mmol, 1 M in THF). The cooling bath was removed and the reaction mixture was stirred at room temperature overnight. The reaction mixture was poured into a separatory funnel containing saturated NaHCO3 and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography on silica gel (10% EtOAc→30% EtOAc in hexanes) to afford a brown oil. 1H NMR (300 MHz, CDCl3): δ 6.73 (d, J=1.5 Hz, 1H), 6.70 (s, 1H), 6.45 (d, J=1.3 Hz, 1H), 4.31-4.00 (m, 5H), 3.75 (s, 3H), 1.89-1.74 (m, 2H), 1.05-1.02 (m, 1H), 0.93 (t, J=7.3 Hz, 3H), 0.90-0.75 (m, 1H), 0.52-0.49 (m, 2H), 0.35-0.25 (m, 1H); HRMS (ESI) m/z 453.0459 [M+, calcd for C19H21N3O3BrCl 453.0455].

1. customThe cooling bath was removed
2. additionThe reaction mixture was poured into a separatory funnel
3. additioncontaining saturated NaHCO3
4. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified by column chromatography on silica gel (10% EtOAc→30% EtOAc in hexanes)
10. customto afford a brown oil

ORD record

ord-654f0ceec7a34d6296c1a756b82cd47f

Source dataset

uspto-grants-2008_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07319100B2