Formaldehyde → 5-[3-Butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-benzoic acid methyl ester

HRID 402024ノート

反応式

HRID 402024 の反応式
Cl.Cl.[CH3:3][O:4][C:5](=[O:36])[C:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[C:16]([O:18][CH:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)[N:15]=[N:14][C:13]=2[CH2:25][CH2:26][CH2:27][CH3:28])[CH:9]=[CH:8][C:7]=1[O:29][CH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.C=O.O.[C:40](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(=O)C>[CH3:3][O:4][C:5](=[O:36])[C:6]1[CH:11]=[C:10]([C:12]2[CH:17]=[C:16]([O:18][CH:19]3[CH2:20][CH2:21][N:22]([CH3:40])[CH2:23][CH2:24]3)[N:15]=[N:14][C:13]=2[CH2:25][CH2:26][CH2:27][CH3:28])[CH:9]=[CH:8][C:7]=1[O:29][CH:30]1[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]1

参加物

7

反応物 4

HCID 712FormaldehydeHCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 673727635-[3-Butyl-6-(piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-benzoic acid methyl ester dihydrochloride

生成物 1

HCID 584384215-[3-Butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-benzoic acid methyl ester

試薬・触媒・溶媒 2

HCID 176Acetic Acid触媒HCID 6344Dichloromethane溶媒

実験手順

To a solution of 5-[3-butyl-6-(piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-benzoic acid methyl ester dihydrochloride in DCM (6 mL) was added formaldehyde solution in water (37%, 2.26 mmol, 0.168 mL) and 2 drops of acetic acid. Sodium triacetoxyborohydride (3.02 mmol, 674 mg, 95%) was added. The reaction mixture was stirred at room temperature for 1 h and partitioned between ethyl acetate (40 mL) and saturated aq. sodium bicarbonate solution (40 mL). The ethyl acetate layer was separated and dried over sodium sulfate. The crude product was purified by column chromatography on basic alumina using 0-4.5% MeOH in DCM to give 5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-benzoic acid methyl ester. This was converted to the title compound using 4 N HCl in dioxane (296 mg). LCMS: m/z 483 [M+1] 1H NMR (400 MHz, CD3OD) δ 7.86-7.93 (2H, m), 7.65-7.71 (1H, m), 7.34-7.38 (1H, m), 5.38-5.55 (1H, m), 4.61-4.65 (1H, m), 3.89 and 3.89 (3H, s), 3.11-3.65 (6H, m), 2.94 (3H, s), 1.16-2.57 (18H, m), 0.83 (3H, dt).

後処理

  1. custompartitioned between ethyl acetate (40 mL) and saturated aq. sodium bicarbonate solution (40 mL)
  2. customThe ethyl acetate layer was separated
  3. dry with materialdried over sodium sulfate
  4. customThe crude product was purified by column chromatography on basic alumina using 0-4.5% MeOH in DCM

出典と根拠

ORDレコード
ord-af51bc82e72645b99c109feb66dcf866
出典データセット
uspto-grants-2014_06
特許番号
US08741900B2

反応ノート

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