Hydrochloric Acid → HCID 131730537, compound

HRID 401878Notes

Reaction equation

HRID 401878 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][C@H:25]3[C@H:29]([CH2:30][O:31][CH3:32])[CH2:28][NH:27][CH2:26]3)[N:20]=[N:19][C:18]=2[CH2:33][CH2:34][CH2:35][CH3:36])=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C=O.O.[C:40](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClCCl.C(O)(=O)C.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][C@H:25]3[C@H:29]([CH2:30][O:31][CH3:32])[CH2:28][N:27]([CH3:40])[CH2:26]3)[N:20]=[N:19][C:18]=2[CH2:33][CH2:34][CH2:35][CH3:36])=[CH:15][CH:16]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 962WaterHCID 5049666Sodium triacetoxyborohydrideHCID 131730539HCID 131730539, compound

Product 1

HCID 131730537HCID 131730537, compoundYield 153.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the above pyridazine dihydrochloride (0.5 mmol, 267 mg) in dichloromethane (2.0 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 concentrated. The mixture 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 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 (211 mg). LCMS: m/z 477 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.83 and 7.93 (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), 5.20 (2H, s), 4.59-4.63 (2H, m), 3.63-3.95 (4H, m), 3.44 (3H, s), 2.58-3.23 (9H, m), 1.44-1.53 (2H, m), 1.25-1.33 (2H, m), 0.81 (3H, t).

Workup

  1. concentrationthen concentrated
  2. additionThe mixture was then diluted with water/EtOAc
  3. dry with materialdried over Na2SO4
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by silica gel chromatography (DCM to DCM+10% 2N ammonia in MeOH)
  6. customto give a solid, which
  7. waitkept at room temperature for 10 min
  8. customcondensed
  9. customtriturated with hexanes

Sources & evidence

ORD record
ord-2727a86e17574deba050ffbae72e24b3
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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