1,4-Dioxane → HCID 178483333, compound

HRID 2183371Notes

Reaction equation

HRID 2183371 reaction equation
O1C2C=CC=CC=2C=C1C1CCCOC1[N:16]1[C:24]2[C:19](=[CH:20][C:21]([C:25]3[NH:29][N:28]=[C:27]([CH2:30][N:31]([CH3:33])[CH3:32])[N:26]=3)=[CH:22][CH:23]=2)[CH:18]=[N:17]1.O1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>Cl.C(OCC)(=O)C>[O:37]1[C:38]2[CH:39]=[CH:18][CH:19]=[CH:20][C:21]=2[CH:35]=[C:36]1[C:18]1[C:19]2[C:24](=[CH:23][CH:22]=[C:21]([C:25]3[NH:29][N:28]=[C:27]([CH2:30][N:31]([CH3:32])[CH3:33])[N:26]=3)[CH:20]=2)[NH:16][N:17]=1

Participants

5

Reactant 2

HCID 312751,4-DioxaneHCID 178483332HCID 178483332, compound

Product 1

HCID 178483333HCID 178483333, compound

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

([5-(3-Benzo[d]furan-2-yl-1-perhydro-2H-pyran-2-yl(1H-indazol-5-yl))(1H-1,2,4-triazol-3-yl)]methyl)dimethylamine (15 mg, 0.034 mmol) in anhydrous HCl (5.0 mL of a 4 N solution in 1,4-dioxane) was vigorously stirred at ambient temperature for 18 h. The reaction mixture was neutralized with the slow addition of satd. NaHCO3 and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and concentrated in vacuo to give a solid which was redissolved in a minimum amount of ethyl acetate and precipitated with hexanes to give the desired product as an off-white powder. The product was further purified by preparatory HPLC using a 30-80% acetonitrile/water gradient with 0.1% CF3CO2H. Fractions containing the desired product were pooled and evaporated to give a pale yellow solid which was partitioned between ethyl acetate and satd. NaHCO3. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated in vacuo to give a solid which was dissolved in a minimum amount of methanol/ethyl acetate and precipitated with hexanes. The solid was collected, washed with ethyl ether/hexanes and dried under vacuum to afford the desired product as a pale solid (5.0 mg, 41% yield) 1H NMR (DMSO-d6) δ 8.9 (s, 1H), 8.14 (dd, 1H), 7.8-7.6 (m, 3H), 7.46 (s, 1H), 7.4-7.26 (m, 2H), 4.65 (s, 2H), 1.85 (s, 6H); ES-MS (m/z) 359 [M+H]+.

Workup

  1. additionThe reaction mixture was neutralized with the slow addition of satd
  2. extractionNaHCO3 and extracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customto give a solid which
  7. customprecipitated with hexanes

Sources & evidence

ORD record
ord-271fe052f82b4a308ad3e17c663739cc
Source dataset
uspto-grants-2005_05
Patent number
US06897231B2

Reaction notes

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