Hydrochloric Acid → HCID 67373987, compound

HRID 1971889Notes

Reaction equation

HRID 1971889 reaction equation
[ClH:1].Cl.[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[CH:22]=[C:21]([O:23][CH2:24][CH:25]3[CH2:29][CH2:28][NH:27][CH2:26]3)[N:20]=[N:19][C:18]=2[CH2:30][CH2:31][CH2:32][CH3:33])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C=O.O.[C:37](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl.C(O)(=O)C.O.CCOC(C)=O.C([O-])(O)=O.[Na+].CCOCC>[ClH:1].[ClH:1].[CH2:3]([O:10][C:11]1[CH:12]=[CH:13][C:14]([C:17]2[CH:22]=[C:21]([O:23][CH2:24][CH:25]3[CH2:29][CH2:28][N:27]([CH3:37])[CH2:26]3)[N:20]=[N:19][C:18]=2[CH2:30][CH2:31][CH2:32][CH3:33])=[CH:15][CH:16]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

11

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 67375265HCID 67375265, compound

Product 1

HCID 67373987HCID 67373987, compoundYield 154.6%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolventHCID 22728543Water ethylacetateSolvent

Procedure

To a solution of 4-(4-benzyloxy-phenyl)-3-butyl-6-(pyrrolidin-3-ylmethoxy)-pyridazine dihydrochloride (0.3 mmol, 147 mg) in dichloromethane (2 mL) was added formaldehyde solution in water (37%, 10 mmol, 1.0 mL), and 2 drops of acetic acid. Then sodium triacetoxyborohydride (10 mmol, 2.12 g) 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 solvent was removed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 2N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (117 mg). LCMS: m/z 433 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.82 (1H, s), 7.45-7.55 (4H, m), 7.36-7.40 (2H, m), 7.31-7.35 (1H, m), 7.21-7.24 (2H, m), 5.20 (2H, s), 4.43 (2H, d), 3.57-3.62 (2H, m), 3.05-3.17 (3H, m), 2.87 (3H, s), 2.14-2.30 (2H, m), 1.70-1.81 (2H, m), 1.45-1.53 (2H, m), 1.23-1.33 (2H, m), 0.81 (3H, t).

Workup

  1. customcondensed
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH)
  4. customto give a colorless sticky solid, which
  5. waitkept at room temperature for 10 min
  6. customcondensed
  7. customtriturated with hexanes

Sources & evidence

ORD record
ord-384d97d1f6154a1a924c9be2950195d4
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

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