1,1,3,3-Tetramethylguanidine → Methyl 3-(4-(6-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)propanoate

HRID 922369노트

반응식

HRID 922369 반응식
Cl.Cl.[N:3]1([CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.F[C:16]1[N:21]=[C:20]([C:22]2[NH:31][C:30](=[O:32])[C:29]3[C:24](=[CH:25][C:26]([O:35][CH3:36])=[CH:27][C:28]=3[O:33][CH3:34])[N:23]=2)[CH:19]=[CH:18][CH:17]=1.CN(C)C(N(C)C)=N>CS(C)=O.O>[CH3:34][O:33][C:28]1[CH:27]=[C:26]([O:35][CH3:36])[CH:25]=[C:24]2[C:29]=1[C:30](=[O:32])[NH:31][C:22]([C:20]1[N:21]=[C:16]([N:6]3[CH2:7][CH2:8][N:3]([CH2:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH2:4][CH2:5]3)[CH:17]=[CH:18][CH:19]=1)=[N:23]2

참가 물질

6

반응물 3

HCID 664601,1,3,3-TetramethylguanidineHCID 45792123Methyl 3-(piperazin-1-yl)propanoate dihydrochlorideHCID 1364081482-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

생성물 1

HCID 136408150Methyl 3-(4-(6-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)propanoate수율 66.5%

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

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온도
85 °C

실험 절차

To a stirred suspension of methyl 3-(piperazin-1-yl)propanoate dihydrochloride (0.358 g, 1.46 mmol) and 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.220 g, 0.73 mmol) in dry DMSO (1.5 mL) was added 1,1,3,3-tetramethylguanidine (0.336 g, 2.92 mmol). The resulting mixture was heated at 85° C. for 5 h. After that time the reaction was cooled to rt, diluted with water (20 mL) and extracted with ethyl acetate (3×25 mL). The organic phase was washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol to 97:3 dichloromethane/methanol) to give methyl 3-(4-(6-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)pyridin-2-yl)piperazin-1-yl)propanoate (0.220 g, 66%) as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 10.31 (s, 1H), 7.85 (d, J=7.42 Hz, 1H), 7.62-7.70 (m, 1H), 6.79-6.85 (m, 2H), 6.48 (d, J=2.34 Hz, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.72 (s, 3H), 3.59-3.67 (m, 4H), 2.75-2.83 (m, 2H), 2.54-2.66 (m, 6H); ESI MS m/z 454 [M+H]+.

후처리

  1. temperatureAfter that time the reaction was cooled to rt
  2. extractionextracted with ethyl acetate (3×25 mL)
  3. washThe organic phase was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol to 97:3 dichloromethane/methanol)

출처 및 근거

ORD 기록
ord-01481b6ee0894e5a83b371ea93767eca
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278940B2

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