반응 #2201601

반응 방정식

BOP

(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid

(1R)-N-Methyl-1-[3′-(methyloxy)-4-biphenylyl]-2-(4-morpholinyl)ethanamine

triethylamine

→

title compound

수율 46.2%

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

수율 46.2%

용매

DMF

반응 조건

후처리

1. 1
   여과The reaction mixture was filtered
2. 2
   workup.ADDITIONthe filtrate was added slowly to of H2O (300 mL) with vigorous stirring
3. 3
   기타The precipitate which formed
4. 4
   여과was collected by filtration
5. 5
   기타further purified by silica gel chromatography (120 g Redisep column, silica, 40 um, 60 Å, 80 mL/min
6. 6
   workup.WAIT2% for 20 min
7. 7
   workup.WAIT5% for 10 min
8. 8
   농축The combined fractions were concentrated
9. 9
   기타the resulting residue was triturated with MeOH
10. 10
    여과The white solid was collected by filtration

실험 절차

(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]+.

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