Chloride → Methyl 6-(4-hydroxypiperidin-1-yl)pyridazine-3-carboxylate

HRID 1755232ノート

反応式

HRID 1755232 の反応式
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([OH:10])=[O:9])=[CH:4][CH:3]=1.C[O-].[Na+].[CH3:14]OC1N=NC(C(O)=O)=CC=1.[Cl-].[OH:26][CH:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1.C(N(C(C)C)CC)(C)C>O=S(Cl)Cl.CO.O1CCOCC1>[OH:26][CH:27]1[CH2:32][CH2:31][N:30]([C:2]2[N:7]=[N:6][C:5]([C:8]([O:10][CH3:14])=[O:9])=[CH:4][CH:3]=2)[CH2:29][CH2:28]1

参加物

10

反応物 6

HCID 312ChlorideHCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 64157626-chloropyridazine-3-carboxylic Acid2 回HCID 10942334Sodium MethoxideHCID 122144616-Methoxypyridazine-3-carboxylic acid

生成物 1

HCID 60980224Methyl 6-(4-hydroxypiperidin-1-yl)pyridazine-3-carboxylate収率 6,068.6%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 24386Thionyl Chloride溶媒HCID 312751,4-Dioxane溶媒

実験手順

A solution of 6-chloropyridazine-3-carboxylic acid (0.50 g, 3.2 mmol) in 11 mL of SOCl2 was heated at 75° C. for 2 h and was then concentrated and redissolved in 5 mL of MeOH. To the solution was added a 25% solution of sodium methoxide (0.75 mL, 3.5 mmol, 1.1 eq) in MeOH. The reaction mixture was stirred at room temperature for 20 h and was then quenched with H2O and extracted with dichloromethane. Silica gel flash chromatography (EtOAc/MeOH 90:10) of the residue afford a 2:1 mixture of the 6-chloropyridazine-3-carboxylic acid and 6-methoxypyridazine-3-carboxylic acid (0.160 g). To a solution of the mixture of ester and chloride in 1.9 mL of p-dioxane was added 4-hydroxy piperidine (0.094 g, 93 mmol) followed by diisopropylethylamine (0.49 mL, 2.8 mmol). The mixture was heated at 100° C. for 20 h then concentrated. Purification with silica gel flash chromatography afforded methyl 6-(4-hydroxypiperidin-1-yl)pyridazine-3-carboxylate (0.15 g, 63 mmol).

後処理

  1. concentrationwas then concentrated
  2. dissolutionredissolved in 5 mL of MeOH
  3. customwas then quenched with H2O
  4. extractionextracted with dichloromethane
  5. customSilica gel flash chromatography (EtOAc/MeOH 90:10) of the residue afford
  6. temperatureThe mixture was heated at 100° C. for 20 h
  7. concentrationthen concentrated
  8. customPurification with silica gel flash chromatography

出典と根拠

ORDレコード
ord-aee8372e6551426ba88f83a27e814aea
出典データセット
uspto-grants-2015_10
特許番号
US09169261B2

反応ノート

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