Methylamine → HCID 178483860, compound

HRID 2240005Notes

Reaction equation

HRID 2240005 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.C1COCC1.[CH3:43][NH2:44]>>[CH3:43][NH:44][CH2:26][CH2:25][CH2:24][O:23][C:20]1[CH:21]=[C:22]2[C:17](=[CH:18][CH:19]=1)[NH:16][N:15]=[C:14]2[S:11]([C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)(=[O:13])=[O:12]

Participants

4

Reactant 3

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 178427737HCID 178427737, compound

Product 1

HCID 178483860HCID 178483860, compound

Conditions

Temperature
70 °C

Procedure

A solution of toluene-4-sulfonic acid 3-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-propyl ester (0.422 g, 0.786 mmol) in 2.0 M methylamine in THF (8.0 mL, 16 mmol). was stirred for 15 hours at 70° C. in a sealed tube. After cooling to ambient temperature, the reaction mixture was concentrated and partitioned in ethyl acetate and aqueous sodium bicarbonate. The organic phase was washed with brine. The aqueous phases were extracted with chloroform, and both organic phases were combined and dried with anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography using 0.75% ammonium hydroxide/7.5% methanol in chloroform. Methyl-{3-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-propyl}-amine was obtained as a light yellow foam (0.209 g, 67.2%). Methanol and ethereal hydrochloride were added to the compound. The resulting solution was concentrated and dried for 14 hours at 84° C. in vacuo. The hydrochloride was obtained as a light yellow foam (0.217 g). Mass Spectrum (−EI, [M−H]−) m/z 394. 1HNMR (500 MHz, DMSO-d6): δ14.16 (s, 1H), 8.74-8.76 (m, 1H), 8.67 (s, br, 2H), 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), 7.70-7.75 (m, 1H), 7.54-7.65 (m, 3H), 7.29 (d, 1H, J=2.19 Hz), 7.08-7.11 (m, 1H), 4.09 (t, 2H, J=5.98 Hz), 3.05 (s, br, 2H), 2.55 (s, 3H), 2.05-2.11 ppm (m, 2H). Elemental Analysis for C21H21N3O3S.1.00 mol HCl.0.45 mol H2O: Calcd: C, 57.32; H, 5.25; N, 9.55; Found: C, 57.64; H, 5.33; N, 9.39.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. concentrationthe reaction mixture was concentrated
  3. custompartitioned in ethyl acetate
  4. washThe organic phase was washed with brine
  5. extractionThe aqueous phases were extracted with chloroform
  6. dry with materialdried with anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-8bbaaf992e4c4f14a81e6a0c1e6dd797
Source dataset
uspto-grants-2010_05
Patent number
US07723329B2

Reaction notes

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