Formaldehyde → HCID 53373968, Verbindung

HRID 401897Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 401897
Cl.Cl.[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:15][CH:14]=1)[CH2:4][CH2:5][CH3:6].C=O.O.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(=O)C.O.CCOC(C)=O.C([O-])(O)=O.[Na+]>[CH2:3]([C:7]1[N:8]=[N:9][C:10]([O:26][CH:27]2[CH2:32][CH2:31][N:30]([CH3:36])[CH2:29][CH2:28]2)=[CH:11][C:12]=1[C:13]1[CH:14]=[CH:15][C:16]([O:19][CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[CH:17][CH:18]=1)[CH2:4][CH2:5][CH3:6]

Komponenten

9

Edukt 4

HCID 712FormaldehydeHCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 67375293HCID 67375293, Verbindung

Produkt 1

HCID 53373968HCID 53373968, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 176Acetic AcidKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 516892Sodium BicarbonateLösungsmittelHCID 22728543Water ethylacetateLösungsmittel

Versuchsvorschrift

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (0.2 mmol, 82 mg) in DCM (2 mL) was added formaldehyde solution in water (37%, 2 mmol, 0.2 mL), and 1 drop of acetic acid. Then sodium triacetoxyborohydride (2 mmol, 424 mg) was added, and the mixture was stirred at room temperature for 0.5 hour then condensed. It was then diluted with water/EtOAc and neutralized with NaHCO3 powder. The organic layers were combined and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH) to provide 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(1-methyl-piperidin-4-yloxy)-pyridazine. The solid was dissolved in 1 mL DCM, 2N HCl in ether (1 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (79 mg). LCMS: m/z 425 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.78 and 7.86 (1H, s), 7.45-7.50 (2H, m), 7.11-7.15 (2H, m), 5.35-5.53 (1H, m), 4.42-4.49 (1H, m), 3.24-3.69 (4H, m), 3.12-3.17 (2H, m), 2.94 (3H, s), 1.90-2.58 (6H, m), 1.78-1.86 (2H, m), 1.34-1.64 (8H, m), 1.25-1.32 (2H, m), 0.82 (3H, t).

Aufarbeitung

  1. customcondensed
  2. dry with materialdried over Na2SO4
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH)

Quellen und Nachweise

ORD-Eintrag
ord-b282ccc10a264e1e8a3bb166aa4f0ffb
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08741900B2

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