반응 #1009567

반응 방정식

2-amino-4,6-difluorobenzamide

6-(4-isopropylpiperazin-1-yl)picolinaldehyde

5,7-dimethoxy-2-(6-(4-(2-(methylsulfonyl)ethyl)piperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one

p-toluenesulfonic acid

NaHSO3

→

title compound

수율 20.5%

5,7-Difluoro-2-(6-(4-isopropylpiperazin-1-yl)pyridin-2-yl)quinazolin-4(3H)-one

수율 20.5%

용매

DMA

반응 조건

후처리

1. 1
   기타The mixture was partitioned between water (25 mL) and CH2Cl2 (25 mL)
2. 2
   기타The layers were separated
3. 3
   건조the organic phase was dried over sodium sulfate
4. 4
   여과filtered
5. 5
   기타The solvent was removed under reduced pressure
6. 6
   기타the residue was purified by silica gel chromatography
7. 7
   세척eluting with 0-5% MeOH in CH2Cl2

실험 절차

A mixture of 2-amino-4,6-difluorobenzamide (7, 330 mg, 1.70 mmol), 6-(4-isopropylpiperazin-1-yl)picolinaldehyde (8, Scheme 6, 330 mg, 1.42 mmol), p-toluenesulfonic acid (590 mg, 3.12 mmol), NaHSO3 (370 mg, 3.55 mmol) and DMA (15 mL) was heated for 24 h at 110° C. under nitrogen. The mixture was partitioned between water (25 mL) and CH2Cl2 (25 mL) and shaken vigorously. The layers were separated and the organic phase was dried over sodium sulfate and filtered. The solvent was removed under reduced pressure and the residue was purified by silica gel chromatography eluting with 0-5% MeOH in CH2Cl2 to provide the title compound (112 mg, 20%): 1H NMR (500 MHz, CDCl3) δ 10.59 (s, 1H), 7.85 (d, J=7.3 Hz, 1H), 7.67 (dd, J=7.3, 8.5 Hz, 1H), 7.30-7.26 (m, 1H), 6.93-6.89 (m, 1H), 6.86 (d, J=8.5 Hz, 1H), 3.69-3.60 (m, 4H), 2.82-2.73 (m, 1H), 2.71-2.66 (m, 4H), 1.12 (s, 3H), 1.11 (s, 3H).

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