1,1,3,3-Tetramethylguanidine → 2-(6-(4-(1-hydroxypropan-2-yl)piperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 1519419ノート

反応式

HRID 1519419 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.Cl.Cl.[N:25]1([CH:31]([CH3:34])[CH2:32][OH:33])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.CN(C)C(N(C)C)=N>CS(C)=O.O>[OH:33][CH2:32][CH:31]([N:25]1[CH2:30][CH2:29][N:28]([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)[CH2:27][CH2:26]1)[CH3:34]

参加物

6

反応物 3

HCID 664601,1,3,3-TetramethylguanidineHCID 119720442-(Piperazin-1-yl)propan-1-ol dihydrochlorideHCID 1364081482-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

生成物 1

HCID 1362488362-(6-(4-(1-hydroxypropan-2-yl)piperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one収率 54.4%

試薬・触媒・溶媒 2

HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

反応条件

温度
85 °C

実験手順

A mixture of 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.202 g, 0.67 mmol), 2-(piperazin-1-yl)propan-1-ol dihydrochloride (0.292 g, 1.34 mmol) and 1,1,3,3-tetramethylguanidine (0.310 g, 2.69 mmol) in dry DMSO (1.5 mL) was heated at 85° C. for 6 h. After that time the reaction was cooled to rt, diluted with water (15 mL) and extracted with ethyl acetate (2×30 mL). The combined organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 97:3 dichloromethane/methanol to 95:5 dichloromethane/methanol) to give 2-(6-(4-(1-hydroxypropan-2-yl)piperazin-1-yl)pyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.155 g, 54%) as a yellow solid: mp 202-204° C.; 1H NMR (400 MHz, CDCl3) δ 10.30 (s, 1H), 7.87 (d, J=7.42 Hz, 1H), 7.64-7.72 (m, 1H), 6.79-6.88 (m, 2H) 6.49 (d, J=2.34 Hz, 1H) 3.99 (s, 3H), 3.94 (s, 3H), 3.61-3.72 (m, 4H), 3.38-3.52 (m, 2H), 2.89-2.99 (m, 1H), 2.78-2.88 (m, 2H), 2.54-2.64 (m, 2H), 0.97 (d, J=6.64 Hz, 3H); ESI MS m/z 426 [M+H]+.

後処理

  1. temperatureAfter that time the reaction was cooled to rt
  2. extractionextracted with ethyl acetate (2×30 mL)
  3. washThe combined organic phase was washed with 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, 97:3 dichloromethane/methanol to 95:5 dichloromethane/methanol)

出典と根拠

ORDレコード
ord-ed705a527b1044d5bbc8c7fd60b2497f
出典データセット
uspto-grants-2015_07
特許番号
US09073878B2

反応ノート

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