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N,N-Dimethylaniline → 4-Chloro-2-(chloromethyl)quinazoline

HRID 1436268
ノート
印刷プレビュー

反応式

HRID 1436268 の反応式
[Cl:1][CH2:2][C:3]1[N:12]=[C:11](N(C2C=CC(OC)=CC=2)C)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.[Cl:23]CC1NC(=O)C2C(=CC=CC=2)N=1.P(Cl)(Cl)(Cl)=O.CN(C)C1C=CC=CC=1>C(Cl)(Cl)Cl>[Cl:23][C:11]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=[C:3]([CH2:2][Cl:1])[N:12]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 11358914(2-Chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amineHCID 1354173742-(chloromethyl)quinazolin-4(3H)-one

生成物 1

HCID 131575204-Chloro-2-(chloromethyl)quinazoline

試薬・触媒・溶媒 1

HCID 6212
Chloroform
溶媒

実験手順

(2-Chloromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine: A mixture of 2-chloromethyl-quinazolin-4(3H)-one (256 mg, 1.32 mmol), phosphoryl chloride (1.23 ml, 13.2 mmol) and N,N-dimethylaniline (0.34 ml, 2.64 mmol) in chloroform (10 ml) was heated under reflux for 4 h. The reaction mixture was poured onto ice and extracted by ethyl acetate. The solvent was evaporated, and the residue was purified by column chromatography on silica gel with acetate and hexane (1:1) as eluent, yielding 180 mg of 4-chloro-2-chloromethyl-quinazoline. The intermediate (170 mg, 0.80 mmol) and (4-methoxy-phenyl)-methylamine (131.7 mg, 0.96 mmol) in isopropyl alcohol (5 ml) with concentrated HCl (0.05 ml) was stirred at room temperature overnight. The precipitation was formed and collected by filtration, then washed and dried to give 231 mg (92%) of the title compound. 1H NMR (CDCl3): 7.82 (d, J=8.7 Hz, 1H), 7.59-7.53 (m, 1H), 7.15-7.12 (m, 2H), 7.03-7.00 (m, 2H), 6.95-6.91 (m, 2H), 4.73 (s, 2H), 3.85 (s, 3H), 3.62 (s, 3H).

後処理

  1. temperaturewas heated
  2. temperatureunder reflux for 4 h
  3. additionThe reaction mixture was poured onto ice
  4. extractionextracted by ethyl acetate
  5. customThe solvent was evaporated
  6. customthe residue was purified by column chromatography on silica gel with acetate and hexane (1:1) as eluent

出典と根拠

ORDレコード
ord-43291879f11c458da704e9b360f85845
出典データセット
uspto-grants-2009_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07618975B2

反応ノート

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