Formaldehyde → HCID 67373118, compound

HRID 1971947Notes

Reaction equation

HRID 1971947 reaction equation
[ClH:1].[CH2:2]([C:6]1[N+:7]([O-:32])=[N:8][C:9]([O:25][CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:10][C:11]=1[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[CH:14][CH:13]=1)[CH2:3][CH2:4][CH3:5].C=O.O.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(=O)C>[ClH:1].[CH2:2]([C:6]1[N+:7]([O-:32])=[N:8][C:9]([O:25][CH:26]2[CH2:31][CH2:30][N:29]([CH3:36])[CH2:28][CH2:27]2)=[CH:10][C:11]=1[C:12]1[CH:13]=[CH:14][C:15]([O:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[CH:16][CH:17]=1)[CH2:3][CH2:4][CH3:5]

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 67371479HCID 67371479, compound

Product 1

HCID 67373118HCID 67373118, compoundYield 89.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(piperidin-4-yloxy)-pyridazine 2-oxide hydrochloride (0.162 mmol, 74.8 mg) in DCM (1.5 mL) was added formaldehyde solution in water (37%, 0.5 mmol, 0.372 mL), and 1 drop of acetic acid. It was stirred for 80 min. and sodium triacetoxyborohydride (0.65 mmol, 145 mg, 95%) was added. The reaction mixture was stirred at room temperature for 80 min. and partitioned between ethyl acetate (8 mL) and saturated aq. sodium bicarbonate solution (8 mL). The ethyl acetate layer was separated and dried over sodium sulfate. The organic solvent was removed in vacuo and the residue was dissolved in DCM and treated with 4 N HCl in dioxane. The organic solvents were removed in vacuo and the residue was triturated with anhydrous diethyl ether and hexanes. The off-white solid was dried overnight under high vacuum to provide the title compound (69.3 mg). LCMS: m/z 441 [M+1] 1H NMR (400 MHz, CD3OD) δ 7.28-7.32 (2H, m), 7.05-7.07 (2H, m), 6.79 and 6.88 (1H, s), 5.15-5.34 (1H, m), 4.38-4.43 (1H, m), 3.23-3.65 (4H, m), 2.92 (3H, s), 2.80-2.84 (2H, m), 2.47-2.56 (1H, m), 2.38 (1H, d), 2.08-2.21 (1H, m), 1.89-2.05 (3H, m), 1.81 (2H, m), 1.21-1.66 (10H, m) 0.82 (3H, t).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 80 min.
  2. custompartitioned between ethyl acetate (8 mL) and saturated aq. sodium bicarbonate solution (8 mL)
  3. customThe ethyl acetate layer was separated
  4. dry with materialdried over sodium sulfate
  5. customThe organic solvent was removed in vacuo
  6. dissolutionthe residue was dissolved in DCM
  7. additiontreated with 4 N HCl in dioxane
  8. customThe organic solvents were removed in vacuo
  9. customthe residue was triturated with anhydrous diethyl ether and hexanes
  10. customThe off-white solid was dried overnight under high vacuum

Sources & evidence

ORD record
ord-4296dc85385a45bab9d1e98e266e3fb2
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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