Potassium Carbonate → 2-(6-(4-isobutylpiperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 922363노트

반응식

HRID 922363 반응식
F[C:2]1[N:7]=[C:6]([C:8]2[NH:17][C:16](=[O:18])[C:15]3[C:10](=[CH:11][C:12]([O:21][CH3:22])=[CH:13][C:14]=3[O:19][CH3:20])[N:9]=2)[CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[CH2:29]([N:33]1[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1)[CH:30]([CH3:32])[CH3:31].CN(C)C(=O)C>CN(C)C=O.C(OCC)(=O)C>[CH2:29]([N:33]1[CH2:38][CH2:37][N:36]([C:2]2[N:7]=[C:6]([C:8]3[NH:17][C:16](=[O:18])[C:15]4[C:10](=[CH:11][C:12]([O:21][CH3:22])=[CH:13][C:14]=4[O:19][CH3:20])[N:9]=3)[CH:5]=[CH:4][CH:3]=2)[CH2:35][CH2:34]1)[CH:30]([CH3:32])[CH3:31]

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 31374DimethylacetamideHCID 20520521-(2-Methylpropyl)piperazineHCID 1364081482-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

생성물 1

HCID 1362488332-(6-(4-isobutylpiperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one수율 34.1%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

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온도
110 °C

실험 절차

To a suspension of 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.108 g, 0.36 mmol) in N,N-dimethylformamide (1.5 mL) was added K2CO3 (0.15 g, 1.07 mmol) and 1-isobutyl-piperazine (88.9 μL, 0.54 mmol). The resulting mixture was heated at 110° C. for 6 h. After that time N,N-dimethylacetamide (1.5 mL) was added and heating was continued for 20 h. After that time the reaction mixture was cooled to rt, diluted with ethyl acetate and filtered. The filtrate was concentrated under reduced pressure and the residue was washed with water, and dried under high vacuum. The product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol) to give 2-(6-(4-isobutylpiperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.052 g, 34%) as a yellow solid: mp 188-189° C.; 1H NMR (400 MHz, CDCl3) δ 10.33 (br s, 1H), 7.83 (d, J=7.42 Hz, 1H), 7.65 (dd, J=8.59, 7.42, 1H), 6.76-6.88 (m, 2H), 6.48 (d, J=2.34 Hz, 1H), 3.99 (s, 3H), 3.94 (s, 3H), 3.64 (t, J=4.88 Hz, 4H), 2.55 (t, J=4.88 Hz, 4H), 2.17 (d, J=7.42 Hz, 2H), 1.75-1.95 (m, 1H), 0.95 (d, J=6.64 Hz, 6H); ESI MS m/z 424 [M+H]+.

후처리

  1. temperatureheating
  2. temperatureAfter that time the reaction mixture was cooled to rt
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. washthe residue was washed with water
  6. customdried under high vacuum
  7. customThe product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol)

출처 및 근거

ORD 기록
ord-5472da6ca0d7411c998c977d79b58145
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278940B2

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