Triethylamine → 2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methyl-N-[(1R)-1-[3'-(methyloxy)-4-biphenylyl]-2-(4-morpholinyl)ethyl]acetamide

(1R)-N-Methyl-1-[3′-(methyloxy)-4-biphenylyl]-2-(4-morpholinyl)ethanamine (3.3 g, 10 mmol) was dissolved in 100 mL of DMF at room temperature with magnetic stirring. The resulting solution was treated with (6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid (4.3 g, 12 mmol, with 23 wt % LiCl) followed by triethylamine (2.8 mL, 20 mmol) and BOP (5.3 g, 12 mmol). The reaction mixture was maintained at room temperature for 16 h. The reaction mixture was filtered and the filtrate was added slowly to of H2O (300 mL) with vigorous stirring. The precipitate which formed was collected by filtration and further purified by silica gel chromatography (120 g Redisep column, silica, 40 um, 60 Å, 80 mL/min, A: MeOH (with 10% NEt3), B: CH2Cl2, A: 1% for 20 min, 2% for 20 min, 5% for 10 min; detection at 254 nm). The combined fractions were concentrated, and the resulting residue was triturated with MeOH. The white solid was collected by filtration to give the title compound (2.7 g, 46%). MS (ES) m/e 585 [M+H]+.

1. filtrationThe reaction mixture was filtered
2. additionthe filtrate was added slowly to of H2O (300 mL) with vigorous stirring
3. customThe precipitate which formed
4. filtrationwas collected by filtration
5. customfurther purified by silica gel chromatography (120 g Redisep column, silica, 40 um, 60 Å, 80 mL/min
6. wait2% for 20 min
7. wait5% for 10 min
8. concentrationThe combined fractions were concentrated
9. customthe resulting residue was triturated with MeOH
10. filtrationThe white solid was collected by filtration

ORD record

ord-735e148a5a9a459bb7ad54c3bb526444

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07432258B2