Pentylamine → 6-Chloropyridazine-3-carboxylic acid methylpentyl amide

HRID 1171801ノート

反応式

HRID 1171801 の反応式
O.O=[C:3]1[NH:8][N:7]=[C:6]([C:9]([OH:11])=O)[CH:5]=[CH:4]1.S(Cl)([Cl:14])=O.[CH2:16](N)[CH2:17][CH2:18]CC.C([N:24]([CH2:27]C)[CH2:25][CH3:26])C>C(Cl)(Cl)Cl.CN(C=O)C>[CH3:27][N:24]([CH2:25][CH2:26][CH2:16][CH2:17][CH3:18])[C:9]([C:6]1[N:7]=[N:8][C:3]([Cl:14])=[CH:4][CH:5]=1)=[O:11]

参加物

7

反応物 4

HCID 8060PentylamineHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 27746516-Hydroxy-3-pyridazinecarboxylic acid monohydrate

生成物 1

HCID 608583786-Chloropyridazine-3-carboxylic acid methylpentyl amide収率 99%

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a mixture of 6-oxo-1,6-dihydropyridazine-3-carboxylic acid monohydrate (3.50 g, 22.1 mmol) in chloroform (110 mL) was added thionyl chloride (8.1 mL, 110 mmol) then catalytic amount of DMF (0.6 mL). The reaction mixture was heated at reflux for 20 hours during this time reaction mixture turn to dark green. After cooling the solvent was removed in vacuo. The crude material was dried under high vacuum for 30 minutes. The residue dissolved in dichloromethane (110 mL) was added dropwise to a solution of amyl amine (3.84 mL, 33.1 mmol) and triethylamine (5.60 mL, 40.2 mmol) at 0° C. The reaction mixture was stirred at room temperature for 2 hours. The organic layer was washed with water, dried over Na2SO4, filtered, and concentrated. The crude material was purified by column chromatography eluting with ethyl acetate:hexane (4:1) to obtain 6-chloropyridazine-3-carboxylic acid methylpentyl amide (4.8 g, 99%). M.p. 98-101° C. 1H NMR (300 MHz, CDCl3) δ 8.28 (d, J=7.2 Hz, 1H), 8.05 (s, br., 1H), 7.68 (d, J=7.2 Hz, 1H), 3.51 (q, J=5.6 Hz, 2H), 1.69-1.63 (m, 2H), 0.90 (t, J=5.6 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 161.5, 158.9, 151.8, 129.4, 128.1, 39.8, 29.1, 29.1, 22.4, 14.0. MS (ES+) m/z 228 (M+1).

後処理

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 20 hours during this time reaction mixture turn to dark green
  3. temperatureAfter cooling the solvent
  4. customwas removed in vacuo
  5. dry with materialThe crude material was dried under high vacuum for 30 minutes
  6. dissolutionThe residue dissolved in dichloromethane (110 mL)
  7. washThe organic layer was washed with water
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude material was purified by column chromatography
  12. washeluting with ethyl acetate:hexane (4:1)

出典と根拠

ORDレコード
ord-0fd9aedae9444159b89809fed68c31d8
出典データセット
uspto-grants-2010_11
特許番号
US07829712B2

反応ノート

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