Water → HCID 178474742, compound

HRID 2368164Notes

Reaction equation

HRID 2368164 reaction equation
[N:1]([CH:4]([CH3:27])[CH2:5][CH2:6][C@H:7]1[CH2:12][CH2:11][C@H:10]([N:13]2[CH:21]=[C:20]3[C:15]([CH:16]=[C:17]([O:22][CH2:23][CH:24]4[CH2:26][CH2:25]4)[CH:18]=[CH:19]3)=[N:14]2)[CH2:9][CH2:8]1)=[N+]=[N-].C1(P([C:41]2[CH:46]=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH2:47]>C1COCC1>[CH:24]1([CH2:23][O:22][C:17]2[CH:18]=[CH:19][C:20]3[C:15]([CH:16]=2)=[N:14][N:13]([C@H:10]2[CH2:11][CH2:12][C@H:7]([CH2:6][CH2:5][CH:4]([NH:1][C:46](=[O:47])[CH3:41])[CH3:27])[CH2:8][CH2:9]2)[CH:21]=3)[CH2:26][CH2:25]1

Participants

5

Reactant 3

HCID 962WaterHCID 11776TriphenylphosphineHCID 178445666HCID 178445666, compound

Product 1

HCID 178474742HCID 178474742, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-[trans-4-(3-azidobutyl)cyclohexyl]-6-(cyclopropylmethoxy)-2H-indazole (2.45 g), triphenylphosphine (1.75 g), water (30 mL) and THF (30 mL) was stirred at room temperature for 3 days. The organic solvent was evaporated under reduced pressure, and the obtained aqueous solution was acidified with 6N hydrochloric acid (pH=1), and washed twice with diethyl ether. The aqueous solution was basified with potassium carbonate and extracted with a mixed solvent of ethyl acetate/THF (10/1). The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in pyridine (30 mL), and acetic anhydride (3.15 mL) was added at room temperature. The reaction mixture was stirred at room temperature for 3 hr, and the solvent was evaporated under reduced pressure. The residue was diluted with 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate, ethyl acetate/methanol), and the obtained solid was recrystallized from hexane/ethyl acetate to give the title compound (1.29 g) as colorless crystals.

Workup

  1. customThe organic solvent was evaporated under reduced pressure
  2. washwashed twice with diethyl ether
  3. extractionextracted with a mixed solvent of ethyl acetate/THF (10/1)
  4. washThe combined organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe residue was dissolved in pyridine (30 mL)
  8. additionacetic anhydride (3.15 mL) was added at room temperature
  9. stirringThe reaction mixture was stirred at room temperature for 3 hr
  10. customthe solvent was evaporated under reduced pressure
  11. additionThe residue was diluted with 1N hydrochloric acid
  12. extractionthe mixture was extracted with ethyl acetate
  13. washThe organic layer was washed with saturated brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe residue was purified by silica gel chromatography (hexane/ethyl acetate, ethyl acetate/methanol)
  17. customthe obtained solid was recrystallized from hexane/ethyl acetate

Sources & evidence

ORD record
ord-7752409b10cc4afeb822d6b8ff02556e
Source dataset
uspto-grants-2014_04
Patent number
US08703758B2

Reaction notes

Loading…