Ammonia → HCID 178511387, compound

HRID 2239999Notes

Reaction equation

HRID 2239999 reaction equation
[NH3:1].[C:2]1([S:8]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][CH2:22]OS(C4C=CC(C)=CC=4)(=O)=O)[CH:18]=3)[NH:13][N:12]=2)(=[O:10])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+]>C1COCC1>[C:2]1([S:8]([C:11]2[C:19]3[C:14](=[CH:15][CH:16]=[C:17]([O:20][CH2:21][CH2:22][NH2:1])[CH:18]=3)[NH:13][N:12]=2)(=[O:10])=[O:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 222AmmoniaHCID 516892Sodium BicarbonateHCID 178427774HCID 178427774, compound

Product 1

HCID 178511387HCID 178511387, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Over five different reactions, liquid ammonia (about 10 mL) was added to a −78° C. solution of toluene-4-sulfonic acid 2-(3-benzenesulfonyl-1H-indazol-5-yloxy)-ethyl ester (1.72 g, 3.63 mmol) in THF (48 mL). This was usually allowed to warm to ambient temperature. This was heated in sealed tube for about 16-35 hours at 70-100° C. After cooling to about ambient temperature, the combined reaction mixtures were then poured into excess sodium bicarbonate solution and extracted with chloroform or methylene chloride. The organic phase was washed with brine, dried with anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chlormatography with 0.75% ammonium hydroxide/7.5% methanol in chloroform. The residue was further purified by HPLC using 30-80% (chloroform/methanol(8:2)/TEA) in heptane/TEA. Concentrating and drying yielded 2-(3-benzenesulfonyl-1H-indazol-5-yloxy)-ethylamine as a white solid to which was added methanol and ethereal hydrochloride. Concentration and drying for 30 hours in vacuo at 83° C. yielded the hydrochloride as a cream-colored solid (0.0951 g, 7.4%): MP: >300° C.; Mass Spectrum (−EI, [M−H]−) m/z 316. 1HNMR (500 MHz, DMSO-d6): δ14.24(s, 1H), 8.09 (br,s, 3H), 7.96-7.98 (m, 2H), 7.56-7.68 (m, 4H), 7.39 (d, 1H, J=2.20 Hz), 7.17 (dd, 1H, J=9.15 Hz and 2.32 Hz), 4.22-4.25 (m, 2H), 3.20-3.24 ppm (m, 2H). Elemental Analysis for C15H15N3O3S.1.00 mol HCl.0.85 mol H2O: Calcd: C, 48.81; H, 4.83; N, 11.38; Found: C, 48.65; H, 4.77; N, 11.00.

Workup

  1. temperatureThis was heated in sealed tube for about 16-35 hours at 70-100° C
  2. temperatureAfter cooling to about ambient temperature
  3. customthe combined reaction mixtures
  4. extractionextracted with chloroform or methylene chloride
  5. washThe organic phase was washed with brine
  6. dry with materialdried with anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chlormatography with 0.75% ammonium hydroxide/7.5% methanol in chloroform
  10. customThe residue was further purified by HPLC
  11. concentrationConcentrating
  12. customdrying

Sources & evidence

ORD record
ord-8a3daba288404a568dfde94762731151
Source dataset
uspto-grants-2010_05
Patent number
US07723329B2

Reaction notes

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