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

HRID 2062172ノート

反応式

HRID 2062172 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 241Benzene溶媒HCID 6344Dichloromethane溶媒

実験手順

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) δ 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)

後処理

  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

出典と根拠

ORDレコード
ord-6ebbc7f83ef640c2a3f91dca808d3d16
出典データセット
uspto-grants-2012_10
特許番号
US08283354B2

反応ノート

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