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

HRID 2168743Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2168743
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]

Komponenten

9

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 176Acetic AcidLösungsmittelHCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 21908982Water methylene chlorideLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-90ab0429b3414b2cb3ae5ee9477a0b7a
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045461B2

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