2,6-Lutidine → 6-chloro-2-[4-(2-chlorophenyl)-2-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}pyrimidin-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one

HRID 874194ノート

反応式

HRID 874194 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:13]([C:14](O)=O)=[CH:12][N:11]=[C:10]([CH2:17][N:18]2[N:22]=[N:21][C:20]([C:23]([F:26])([F:25])[F:24])=[N:19]2)[N:9]=1.N1C(C)=CC=CC=1C.CS(Cl)(=O)=O.[NH2:40][C:41]1[C:49]([CH3:50])=[CH:48][C:47]([Cl:51])=[CH:46][C:42]=1[C:43]([OH:45])=[O:44]>C(#N)C>[Cl:51][C:47]1[CH:48]=[C:49]([CH3:50])[C:41]2[N:40]=[C:14]([C:13]3[C:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])=[N:9][C:10]([CH2:17][N:18]4[N:22]=[N:21][C:20]([C:23]([F:24])([F:26])[F:25])=[N:19]4)=[N:11][CH:12]=3)[O:44][C:43](=[O:45])[C:42]=2[CH:46]=1

参加物

6

反応物 4

HCID 79372,6-Lutidine2 回HCID 31297Methanesulfonyl chloride2 回HCID 116440442-Amino-5-chloro-3-methylbenzoic acidHCID 671252154-(2-chlorophenyl)-2-[5-(trifluoromethyl)-2H-tetrazol-2-yl]methylpyrimidine-5-carboxylic acid

生成物 1

HCID 585643856-chloro-2-[4-(2-chlorophenyl)-2-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}pyrimidin-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒4 回

反応条件

温度
0 °C

実験手順

At RT, 385 mg (1.30 mmol) of 4-(2-chlorophenyl)-2-{[5-(trifluoromethyl)-2H-tetrazol-2-yl]methyl}pyrimidine-5-carboxylic acid was initially charged in 5 ml of acetonitrile, and 0.27 ml (2.33 mmol) of lutidine was added. With stirring, the solution was then cooled to 0° C., 0.14 ml (1.78 mmol) of methanesulphonyl chloride, dissolved in 2 ml of acetonitrile, was added dropwise and the mixture was stirred at 0° C. for another 15 min. A little at a time, an acetonitrile suspension (3 ml) of 0.53 ml (4.54 mmol) of lutidine and 289 mg (1.56 mmol) of 2-amino-5-chloro-3-methylbenzoic acid was then added to this reaction mixture, and stirring was continued for another 15 min. 0.14 ml (1.78 mmol) of methanesulphonyl chloride, dissolved in 2 ml of acetonitrile, was then added dropwise. The reaction was stirred overnight, with the temperature increasing to RT. The solvent was removed under reduced pressure. The residue was then poured into ice-water and mixed in an ultrasonic bath. The residue was filtered off, again taken up in water and sonicated once more. The residue is filtered off, washed with water and dried under reduced pressure. 708 mg (88% of theory; content 86%) of the desired product were isolated. There was not further purification.

後処理

  1. additionwas added dropwise
  2. stirringthe mixture was stirred at 0° C. for another 15 min
  3. stirringstirring
  4. additionwas then added dropwise
  5. stirringThe reaction was stirred overnight, with the temperature
  6. temperatureincreasing to RT
  7. customThe solvent was removed under reduced pressure
  8. additionThe residue was then poured into ice-water
  9. additionmixed in an ultrasonic bath
  10. filtrationThe residue was filtered off
  11. customsonicated once more
  12. filtrationThe residue is filtered off
  13. washwashed with water
  14. customdried under reduced pressure

出典と根拠

ORDレコード
ord-364366d4267d45da90e3da562366f902
出典データセット
uspto-grants-2015_03
特許番号
US08980886B2

反応ノート

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