Morpholine → HCID 178527282, compound

HRID 2240011Notes

Reaction equation

HRID 2240011 reaction equation
[C:1]1([S:11]([C:14]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([O:23][CH2:24][CH2:25][CH2:26]OS(C4C=CC(C)=CC=4)(=O)=O)[CH:21]=3)[NH:16][N:15]=2)(=[O:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH:38]1[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1>C1COCC1>[N:38]1([CH2:26][CH2:25][CH2:24][O:23][C:20]2[CH:21]=[C:22]3[C:17](=[CH:18][CH:19]=2)[NH:16][N:15]=[C:14]3[S:11]([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)(=[O:12])=[O:13])[CH2:43][CH2:42][O:41][CH2:40][CH2:39]1

Participants

4

Reactant 2

HCID 8083MorpholineHCID 178427737HCID 178427737, compound

Product 1

HCID 178527282HCID 178527282, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of toluene-4-sulfonic acid 3-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-propyl ester (0.080 mg, 0.15 mmol) and morpholine (0.45-0.75 mmol) in THF (10 mL) was stirred at 90° C. for about 2 hours in a sealed tube. After cooling to ambient temperature the reaction mixture was solvent evaporated. It was dissolved in ethyl acetate and washed twice with aqueous sodium bicarbonate. The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography using 0.5% ammonium hydroxide/5.0% methanol in chloroform. 5-(3-Morpholin-4-yl-propoxy)-3-(naphthalene-1-sulfonyl)-1H-indazole as a light yellow solid (74.4 mg, 100%) was obtained. This product was dissolved in methanol, and ethereal hydrochloride was added. Concentrating and drying in vacuo 83° C. for 24 hours yielded the hydrochloride as a yellow foam (74.5 mg, 100%); Mass Spectrum (+EI, [M+H]+) m/z 452. 1HNMR (500 MHz, DMSO-d6): δ14.15 (s, 1H), 10.56-10.62 (br, 1H), 8.75 (d, 1H, J=8.66 Hz), 8.52 (dd, 1H, J=7.44 Hz and 1.22 Hz), 8.27 (d, 1H, J=8.30 Hz), 8.02-8.05 (m, 1H), 7.71-7.75 (m, 1H), 7.54-7.65 (m, 3H), 7.29 (d, 1H, J=2.32 Hz), 7.07-7.10 (m, 1H), 4.10 (t, 2H, J=5.86 Hz), 3.93-3.96 (m, 2H), 3.71-3.77 (m, 2H), 3.43-3.46 (m, 2H), 2.99-3.15 (m, 2H), 2.14-2.22 ppm (m, 2H). Elemental Analysis for C24H25N3O5S.1.00 mol HCl.1.30 mol H2O: Calcd: C, 56.36; H, 5.36; N, 8.22; Found: C, 56.05; H, 5.65; N, 8.09.

Workup

  1. customevaporated
  2. dissolutionIt was dissolved in ethyl acetate
  3. washwashed twice with aqueous sodium bicarbonate
  4. dry with materialThe organic phase was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-5fecb8eb436d416b90e658bd58e2e240
Source dataset
uspto-grants-2010_05
Patent number
US07723329B2

Reaction notes

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