N,N-Dimethylaniline → 4-Chloro-2-(2-fluoro-6-methoxyphenyl)-7-methylquinazoline

HRID 2079260노트

반응식

HRID 2079260 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[C:10]1[NH:19][C:18](=O)[C:17]2[C:12](=[CH:13][C:14]([CH3:21])=[CH:15][CH:16]=2)[N:11]=1.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)[Cl:33].C([O-])(O)=O.[Na+]>C1C=CC=CC=1.C(Cl)Cl>[Cl:33][C:18]1[C:17]2[C:12](=[CH:13][C:14]([CH3:21])=[CH:15][CH:16]=2)[N:11]=[C:10]([C:3]2[C:4]([O:8][CH3:9])=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[N:19]=1

참가 물질

7

반응물 4

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1361215392-(2-fluoro-6-methoxyphenyl)-7-methylquinazolin-4(3H)-one

생성물 1

HCID 586839024-Chloro-2-(2-fluoro-6-methoxyphenyl)-7-methylquinazoline수율 88.4%

시약·촉매·용매 2

HCID 241Benzene용매HCID 6344Dichloromethane용매

실험 절차

Under an N2 atmosphere, 2-(2-fluoro-6-methoxyphenyl)-7-methylquinazolin-4(3H)-one (20 g, 70.35 mmol) was suspended in benzene (300 mL), followed by the addition of N,N-dimethylaniline (26.8 mL, 211.05 mmol), then POCl3 (13.11 mL, 140.7 mmol). The reaction was heated at reflux, and completion of product formation was observed after 1.5 h. After cooling to room temperature, the mixture was slowly poured over 1 liter of ice. The solution was then diluted with CH2Cl2, and the pH was adjusted to 7 using a saturated aqueous NaHCO3 solution. The layers were partitioned, separated and extracted with CH2Cl2. All organic layers were combined, dried over Na2SO4, filtered, and concentrated to a dark oil. The crude material was purified by silica gel chromatography using 75% CH2Cl2/25% hexanes to obtain 4-chloro-2-(2-fluoro-6-methoxyphenyl)-7-methylquinazoline as a yellow solid (18.82 g, 88%). LC/MS: m/z 302.9 (M+H)+ at 3.28 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)). 1H NMR (400 MHz, CDCl3) d 8.22 (d, J=8.5 Hz, 1H), 7.95 (s, 1H), 7.60 (dd, J=8.6, 1.5 Hz, 1H), 7.42-7.40 (m, 1H), 6.86-6.84 (m, 2H), 3.81 (s, 3H), 2.64 (s, 3H) ppm.

후처리

  1. temperatureThe reaction was heated
  2. temperatureat reflux
  3. customThe layers were partitioned
  4. customseparated
  5. extractionextracted with CH2Cl2
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to a dark oil
  9. customThe crude material was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-ebb452173c4d44ef95d6d95a00202d49
출처 데이터셋
uspto-grants-2011_04
특허 번호
US07928107B2

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