Formaldehyde → HCID 53373968, compound

HRID 2168625Notes

Reaction equation

HRID 2168625 reaction equation
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]

Participants

9

Reactant 4

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

Product 1

HCID 53373968HCID 53373968, compound

Reagents, catalysts & solvents 4

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolventHCID 22728543Water ethylacetateSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-bf6430735f8843b4bbf7a0049f3ccce8
Source dataset
uspto-grants-2015_06
Patent number
US09045461B2

Reaction notes

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