Hydrochloric Acid → 6-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-2H-pyridazin-3-one

HRID 1157237ノート

反応式

HRID 1157237 の反応式
[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([CH:9]([C:12]2[N:13]=[N:14][C:15](Cl)=[C:16]([CH:18]([CH3:20])[CH3:19])[CH:17]=2)C#N)=[C:4]([Cl:22])[CH:3]=1.[OH2:23].Cl.[OH-].[Na+]>C(O)(=O)C>[NH2:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([CH2:9][C:12]2[CH:17]=[C:16]([CH:18]([CH3:20])[CH3:19])[C:15](=[O:23])[NH:14][N:13]=2)=[C:4]([Cl:22])[CH:3]=1

参加物

6

反応物 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 59834538(4-Amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile

生成物 1

HCID 598344496-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-2H-pyridazin-3-one収率 76%

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
120 °C

実験手順

A mixture of (4-amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile (45) (6.98 g, 19.63 mmol), water (30 mL), concentrated hydrochloric acid (120 mL) and glacial acetic acid (30 mL) was heated to 120° C. for 24 h. At this time, the reaction was cooled to room temperature and the mixture was poured onto water (250 mL). The pH was made neutral (pH=7) by the addition of a 4N aqueous sodium hydroxide solution. The suspension was placed in the freezer for 15 min. The resulting solids were filtered and washed with water and petroleum ether. The solids were collected and dissolved in hot ethyl acetate. Silica gel 60 (70-230 mesh) was added and the solvent was concentrated under vacuum. The resulting mixture was purified by flash chromatography (Biotage 75S) using silica gel eluted with 40% ethyl acetate in hexanes to 50% ethyl acetate in hexanes containing 0.5% glacial acetic acid. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford 6-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one (46) (4.65 g, 76%) as an off-white solid; LRMS for C14H15Cl2N3O (M+H) m/z=312. Molecular Weight=312.2012; Exact Mass=311.0592

後処理

  1. temperatureAt this time, the reaction was cooled to room temperature
  2. additionthe mixture was poured onto water (250 mL)
  3. filtrationThe resulting solids were filtered
  4. washwashed with water and petroleum ether
  5. customThe solids were collected
  6. dissolutiondissolved in hot ethyl acetate
  7. additionSilica gel 60 (70-230 mesh) was added
  8. concentrationthe solvent was concentrated under vacuum
  9. customThe resulting mixture was purified by flash chromatography (Biotage 75S)
  10. washeluted with 40% ethyl acetate in hexanes to 50% ethyl acetate in hexanes containing 0.5% glacial acetic acid
  11. customThe desired fractions were collected
  12. concentrationconcentrated under vacuum
  13. customto afford a solid which
  14. customwas dried under high vacuum

出典と根拠

ORDレコード
ord-1db641172e4e441e8a4839707f7d85a0
出典データセット
uspto-grants-2010_10
特許番号
US07807674B2

反応ノート

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