Methanol → 1-(4-methoxybenzyl)-7-(3-oxoazetidin-1-yl)-1,5-naphthyridin-2(1H)-one

HRID 509633노트

반응식

HRID 509633 반응식
[CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([N:18]4[CH2:21][CH:20]([OH:22])[CH2:19]4)[CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:23])=[CH:5][CH:4]=1.CCN(CC)CC.S(=O)(=O)=O.N1C=CC=CC=1.CO>CS(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:17]3[C:12](=[N:13][CH:14]=[C:15]([N:18]4[CH2:21][C:20](=[O:22])[CH2:19]4)[CH:16]=3)[CH:11]=[CH:10][C:9]2=[O:23])=[CH:24][CH:25]=1

참가 물질

6

반응물 4

HCID 887MethanolHCID 8471TriethylamineHCID 168533Sulfur trioxide-pyridineHCID 679929881-(4-methoxybenzyl)-7-(3-hydroxyazetidin-1-yl)-1,5-naphthyridin-2(1H)-one

생성물 1

HCID 679930121-(4-methoxybenzyl)-7-(3-oxoazetidin-1-yl)-1,5-naphthyridin-2(1H)-one수율 99.3%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매2회

실험 절차

To a mixture of 1-(4-methoxybenzyl)-7-(3-hydroxyazetidin-1-yl)-1,5-naphthyridin-2(1H)-one (C-6) (2.637 g, 7.81 mmol, 1.0 eq) in DMSO (30 mL) was added Et3N (9 mL, 64.82 mmol, 8.3 eq) and a solution of pyridine sulfur trioxide (8.71 g, 54.7 mmol, 7.0 eq) in DMSO (30 mL) sequentially. The resulting mixture was stirred at RT for 1 h. The reaction was complete based on TLC analysis. The mixture was poured into ice-water (100 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (1:1 to 1:3 petroether/ethyl acetate and then 80:1DCM/MeOH) to afford the desired product 1-(4-methoxybenzyl)-7-(3-oxoazetidin-1-yl)-1,5-naphthyridin-2(1H)-one (C-7) (2.6 g, 99% yield) as a pale solid. HNMR (300 MHz, DMSO-d6) δ: 7.93 (s, 1H), 7.82 (d, J=9.6 Hz, 1H), 7.21 (d, J=9 Hz, 2H), 6.84 (m, 3H), 6.60 (d, J=9.6 Hz, 1H), 5.37 (s, 2H), 4.79 (s, 4H), 3.65 (s, 3H); ESI-MS m/z: 336.1 [M+H]+.

후처리

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe residue was purified by flash column chromatography on silica gel (1:1 to 1:3 petroether/ethyl acetate

출처 및 근거

ORD 기록
ord-d7a93fcb0ee749159304f0a686b93a2b
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096590B2

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