Hydrochloric Acid → HCID 67371462, compound

HRID 1971887Notes

Reaction equation

HRID 1971887 reaction equation
[ClH:1].Cl.[NH:3]1[CH2:6][CH:5]([CH2:7][O:8][C:9]2[N:14]=[N:13][C:12]([CH2:15][CH2:16][CH2:17][CH3:18])=[C:11]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:21][CH:20]=3)[CH:10]=2)[CH2:4]1.C=O.O.[C:36](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+].Cl>ClCCl.C(O)(=O)C.O.CCOC(C)=O.CCOCC>[ClH:1].[ClH:1].[CH2:26]([O:25][C:22]1[CH:21]=[CH:20][C:19]([C:11]2[CH:10]=[C:9]([O:8][CH2:7][CH:5]3[CH2:4][N:3]([CH3:36])[CH2:6]3)[N:14]=[N:13][C:12]=2[CH2:15][CH2:16][CH2:17][CH3:18])=[CH:24][CH:23]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 962WaterHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 67373538HCID 67373538, compound

Product 1

HCID 67371462HCID 67371462, compoundYield 144.1%

Reagents, catalysts & solvents 4

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

Procedure

To a solution of the above pyridazine dihydrochloride (0.3 mmol, 143 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. The mixture was stirred at room temperature for 0.5 hour then condensed, 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 ammonia in MeOH) to give a 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 (106 mg). LCMS: m/z 419 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.84 (1H, s), 7.45-7.55 (4H, m), 7.36-7.40 (2H, m), 7.31-7.35 (1H, m), 7.20-7.24 (2H, m), 5.21 (2H, s), 4.42 (2H, d), 3.63-3.68 (2H, m), 3.02-3.17 (4H, m), 2.87 (3H, s), 2.25-2.33 (1H, m), 1.62-1.74 (2H, m), 1.23-1.33 (2H, m), 0.82 (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 ammonia in MeOH)
  4. customto give a solid, which
  5. waitkept at room temperature for 10 min
  6. customcondensed
  7. customtriturated with hexanes

Sources & evidence

ORD record
ord-1559dfecb6634df0bcd469b0d6503633
Source dataset
uspto-grants-2013_04
Patent number
US08431575B2

Reaction notes

Loading…