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

HRID 1972021노트

반응식

HRID 1972021 반응식
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]

참가 물질

9

반응물 4

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

생성물 1

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

시약·촉매·용매 4

HCID 176Acetic Acid용매HCID 962Water용매HCID 6344Dichloromethane용매HCID 21908982Water methylene chloride용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-94c5c30d3d664914ad519ad7bf2fc6e7
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08431575B2

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