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 1519419노트

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HRID 1519419 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.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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매

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온도
85 °C

실험 절차

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]+.

후처리

  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)

출처 및 근거

ORD 기록
ord-ed705a527b1044d5bbc8c7fd60b2497f
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073878B2

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