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Pyrrolidine → 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)quinolin-4(1H)-one

HRID 525945
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HRID 525945 반응식
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:33])=[C:10]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)[C:11]=2[O:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[C:6](=[O:34])[C:5]([CH:35]=O)=[CH:4]1)[CH3:2].[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CC(O)=O>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([F:33])=[C:10]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[C:11]=2[O:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[C:6](=[O:34])[C:5]([CH2:35][N:37]2[CH2:41][CH2:40][CH2:39][CH2:38]2)=[CH:4]1)[CH3:2]
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6

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HCID 31268PyrrolidineHCID 5049666Sodium triacetoxyborohydrideHCID 867328131-Ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carbaldehyde

생성물 1

HCID 867328141-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)quinolin-4(1H)-one수율 58.8%

시약·촉매·용매 2

HCID 176
Acetic Acid
촉매
HCID 111,2-Dichloroethane용매

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온도
25 °C

실험 절차

To a solution of 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydroquinoline-3-carbaldehyde (15 g, 30.5 mmol) in 1,2-Dichloroethane (DCE) (100 mL) was added pyrrolidine (3.78 mL, 45.8 mmol), sodium triacetoxyborohydride (12.94 g, 61.0 mmol) and AcOH (0.087 mL, 1.526 mmol). The reaction mixture was stirred at 25° C. for 3 h. LCMS showed completion of the reaction. The mixture was extracted with DCM and washed with brine. The organic solution was dried over sodium sulfate and evaporated in vacuo. The crude material was purified by normal phase automatic silica column chromatography (Combiflash RF), using a 40 g golden column and eluting with MeOH/DCM (0-20%). The product was further purified with reverse phase automatic silica column chromatography (Combiflash RF), using a 150 g golden column and eluting with acetonitrile/water (0-60%) to afford 1-ethyl-6-fluoro-7,8-bis((4-methoxybenzyl)oxy)-3-(pyrrolidin-1-ylmethyl)quinolin-4(1H)-one (9.8 g, 17.93 mmol, 58.7% yield) as a yellow solid. LCMS: (M+H)+: 547.4.

후처리

  1. customcompletion of the reaction
  2. extractionThe mixture was extracted with DCM
  3. washwashed with brine
  4. dry with materialThe organic solution was dried over sodium sulfate
  5. customevaporated in vacuo
  6. customThe crude material was purified by normal phase automatic silica column chromatography (Combiflash RF)
  7. washeluting with MeOH/DCM (0-20%)
  8. customThe product was further purified with reverse phase automatic silica column chromatography (Combiflash RF)
  9. washeluting with acetonitrile/water (0-60%)

출처 및 근거

ORD 기록
ord-1f3116bd575b4d428c3a55a1cdd020b7
출처 데이터셋
uspto-grants-2016_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09340556B2

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