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

HRID 922363ノート

反応式

HRID 922363 の反応式
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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
110 °C

実験手順

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]+.

後処理

  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)

出典と根拠

ORDレコード
ord-5472da6ca0d7411c998c977d79b58145
出典データセット
uspto-grants-2016_03
特許番号
US09278940B2

反応ノート

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