Water → HCID 178474138, compound

HRID 1349688Notes

Reaction equation

HRID 1349688 reaction equation
O1CCCCC1[N:7]1[C:15]2[C:10](=[CH:11][C:12]([C:16]3[N:20]=[CH:19][N:18](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[N:17]=3)=[CH:13][CH:14]=2)[C:9]([C:40]2[CH:41]=[C:42]([NH2:46])[CH:43]=[CH:44][CH:45]=2)=[N:8]1.[C:47](OC(=O)C)(=[O:49])[CH3:48].O.[OH-].[Na+]>C(O)(=O)C>[NH:18]1[CH:19]=[N:20][C:16]([C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[NH:7][N:8]=[C:9]3[C:40]2[CH:41]=[C:42]([NH:46][C:47](=[O:49])[CH3:48])[CH:43]=[CH:44][CH:45]=2)=[N:17]1

Participants

6

Reactant 4

HCID 962WaterHCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 211011823-(1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazol-3-yl}phenylamine

Product 1

HCID 178474138HCID 178474138, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution 3-{1-perhydro-2H-pyran-2-yl-5-[1-(triphenylmethyl)(1,2,4-triazol-3-yl)]-1H-indazole-3-yl}phenylamine (0.200 g, 0.63 mmol), in acetic acid (6.0 mL) was added acetic anhydride (0.178 mL, 1.89 mmol). The reaction mixture was heated to reflux temperature for 12 hours. Water was added (10 mL) and the mixture was neutralized with 2.0 N aqueous sodium hydroxide. The product was extracted with ethyl acetate and concentrated to dryness. The crude oil was dissolved in 4 mL of ethanol and treated with 4 mL of commercial solution of hydrogen peroxide and 0.200 mL of 2.0 N aqueous sodium hydroxide. After 3 hours, the solvent was removed under reduced pressure. The resulting oil was dissolved in 5 mL of dimethoxy dimethyl formamide acetal and the solution was heated to reflux temperature for 3 hours. The solvent was removed under reduced pressure and the residue was dissolved in 10 mL of acetic acid and treated with 1 mL of anhydrous hydrazine. The reaction mixture was heated to reflux temperature for 12 hours. After neutralization with aqueous sodium hydroxide (2.0 N), the crude was extracted with ethyl acetate and purified by preparative HPLC (15–80% acetonitrile in water) (0.040 g, 20% over 5 steps): 1H NMR (DMSO-d6) δ 13.4 (br s, 1H), 10.1 (s, 1H), 8.7 (s, 1H), 8.4 (br s, 1H), 8.2 (s, 1H), 8.1 (d, 1H), 7.7 (t, 3H), 7.5 (t, 1H), 2.1 (s, 3H); ES-MS (m/z) 319 [M+1]+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux temperature for 12 hours
  3. extractionThe product was extracted with ethyl acetate
  4. concentrationconcentrated to dryness
  5. dissolutionThe crude oil was dissolved in 4 mL of ethanol
  6. additiontreated with 4 mL of commercial solution of hydrogen peroxide and 0.200 mL of 2.0 N aqueous sodium hydroxide
  7. customthe solvent was removed under reduced pressure
  8. dissolutionThe resulting oil was dissolved in 5 mL of dimethoxy dimethyl formamide acetal
  9. temperaturethe solution was heated
  10. temperatureto reflux temperature for 3 hours
  11. customThe solvent was removed under reduced pressure
  12. dissolutionthe residue was dissolved in 10 mL of acetic acid
  13. additiontreated with 1 mL of anhydrous hydrazine
  14. temperatureThe reaction mixture was heated
  15. temperatureto reflux temperature for 12 hours
  16. extractionAfter neutralization with aqueous sodium hydroxide (2.0 N), the crude was extracted with ethyl acetate
  17. custompurified by preparative HPLC (15–80% acetonitrile in water) (0.040 g, 20% over 5 steps)

Sources & evidence

ORD record
ord-7942d6862d3b45e69ac30f743d23d847
Source dataset
uspto-grants-2007_05
Patent number
US07211594B2

Reaction notes

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