p-Toluenesulfonic acid monohydrate → 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one

HRID 922359노트

반응식

HRID 922359 반응식
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[F:15][C:16]1[N:21]=[C:20]([CH:22]=O)[CH:19]=[CH:18][CH:17]=1.OS([O-])=O.[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C)C(=O)C>[F:15][C:16]1[N:21]=[C:20]([C:22]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][C:9]([O:11][CH3:12])=[CH:8][C:7]=3[O:13][CH3:14])[N:1]=2)[CH:19]=[CH:18][CH:17]=1

참가 물질

6

반응물 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 106067416-Fluoropyridine-2-carboxaldehydeHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium Bisulfite

생성물 1

HCID 1364081482-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one수율 49%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

반응 조건

온도
120 °C

실험 절차

To a solution of 2-amino-4,6-dimethoxybenzamide (0.737 g, 3.76 mmol) and 6-fluoropicolinaldehyde (0.470 g, 3.76 mmol) in N,N-dimethylacetamide (20 mL), NaHSO3 (58.5% SO2 content, 1.0 g, 5.63 mmol) and p-toluenesulfonic acid monohydrate (0.143 g, 0.75 mmol) were added. The reaction was heated at 120° C. for 20 h. After that time the reaction was cooled to rt, concentrated under reduced pressure, diluted with water (50 mL) and saturated NaHCO3 solution was added to adjust the pH to 8. The precipitated solids were collected by filtration, washed with water and dried. The product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol to 97:3 dichloromethane/methanol) to give 2-(6-fluoropyridin-2-yl)-5,7-dimethoxyquinazolin-4(3H)-one (0.550 g, 49%) as a yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 11.34 (s, 1H), 8.28-8.33 (m, 1H), 8.19-8.27 (m, 1H), 7.47 (dd, J=8.01, 1.76 Hz, 1H), 6.82 (d, J=2.34 Hz, 1H), 6.62 (d, J=2.34 Hz, 1H), 3.91 (s, 3H), 3.86 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ −68.08 (d, J=8.03 Hz); ESI MS m/z 302 [M+H]+.

후처리

  1. temperatureAfter that time the reaction was cooled to rt
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with water (50 mL) and saturated NaHCO3 solution
  4. additionwas added
  5. filtrationThe precipitated solids were collected by filtration
  6. washwashed with water
  7. customdried
  8. customThe product was purified by flash column chromatography (silica gel, 99:1 dichloromethane/methanol to 97:3 dichloromethane/methanol)

출처 및 근거

ORD 기록
ord-9dbf94ea01ef4f5dbdb55341c899ff4d
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278940B2

반응 노트

불러오는 중…