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

HRID 2168743ノート

反応式

HRID 2168743 の反応式
Cl.Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:28][CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[C:17]([CH:20]=1)[C:18]#[N:19])[CH2:4][CH2:5][CH3:6].C=O.[C:37](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCl.O.O.C(Cl)Cl.C(O)(=O)C>[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:28][CH:29]2[CH2:34][CH2:33][N:32]([CH3:37])[CH2:31][CH2:30]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[C:17]([CH:20]=1)[C:18]#[N:19])[CH2:4][CH2:5][CH3:6]

参加物

9

反応物 4

HCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 673743785-[3-Butyl-6-(piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-benzonitrile dihydrochloride

生成物 1

HCID 584384325-[3-Butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-benzonitrile

試薬・触媒・溶媒 4

HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 21908982Water methylene chloride溶媒

実験手順

To a solution of 5-[3-butyl-6-(piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-benzonitrile dihydrochloride (19 mg, 0.037 mmol) in dichloromethane (2.0 mL) was added formaldehyde solution in water (37%, 0.2 mL), and 0.1 mL of acetic acid. Then sodium triacetoxyborohydride (200 mg) was added. And the mixture was stirred at room temperature for 10 min then condensed. It was then diluted with water/DCM, neutralized with sat NaHCO3 powder, organic layer was separated washed with water, brine and dried (Na2SO4). The solvent was removed in vacuo and the residue was purified by column chromatography using 5% methanolic solution of ammonia (2.0 M ammonia in methanol) in DCM to get 5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-benzonitrile. This compound was dissolved in DCM (2.0 mL) and 1.0 mL of 4.0 M HCl in dioxane was added. Solvents were evaporated resulting solid was washed with ether and dried to provide the title compound (13 mg, 95%). LCMS: m/z 450 [M+1]. 7.75-7.89 (3H, m), 7.40-7.49 (1H, m), 5.40-5.51 (1H, m), 4.68-4.72 (1H, m), 3.65-3.68 (1H, m), 3.39-3.52 (2H, m), 3.10-3.18 (2H, m), 2.94 (3H, s), 2.54 (1H, d), 2.41 (1H, d), 2.21-2.29 (1H, m), 1.98-2.11 (3H, m), 1.81-1.90 (2H, m), 1.60-1.7 (2H, m), 1.41-1.61 (6H, m), 1.28-1.35 (3H, m), 0.83 (3H, t).

後処理

  1. customcondensed
  2. customwas separated
  3. washwashed with water, brine
  4. dry with materialdried (Na2SO4)
  5. customThe solvent was removed in vacuo
  6. customthe residue was purified by column chromatography

出典と根拠

ORDレコード
ord-90ab0429b3414b2cb3ae5ee9477a0b7a
出典データセット
uspto-grants-2015_06
特許番号
US09045461B2

反応ノート

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