N-Methylethylamine → HCID 178464183, compound

HRID 2240019Notes

Reaction equation

HRID 2240019 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]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.[CH2:37]([NH:39][CH3:40])[CH3:38]>C1COCC1>[CH2:37]([N:39]([CH3:40])[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:12])=[O:13])[CH3:38]

Participants

4

Reactant 2

HCID 12219N-Methylethylamine2×HCID 178427773HCID 178427773, compound

Product 1

HCID 178464183HCID 178464183, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A solution of toluene-4-sulfonic acid 2-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl ester (1.18 g, 2.26 mmol) and ethylmethylamine (2.0 mL, 23 mmol) in THF (20 mL) was stirred for 16 hours at 70° C. in a sealed tube. More ethylmethylamine (2.0 mL, 23 mmol) was added, and the reaction mixture was heated to 80° C. for 20 hours 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, 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. Drying in vacuo at 69° C. for 20 minutes yielded ethyl-methyl-{2-[3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl}-amine as a buff foam (0.409 g, 44.2%). Methanol, chloroform and ethereal hydrochloride were added. The resulting solution was concentrated and dried for 16 hours at 84° C. in vacuo. The hydrochloride was obtained as a buff semi-solid (0.424 g). Mass Spectrum (+EI, [M+H]+) m/z 410. 1HNMR (500 MHz, DMSO-d6): δ14.21 (s, 1H), 10.00-10.01 (s, 1H), 8.74-8.77 (m, 1H), 8.52 (dd, 1H, J=7.44 Hz and 1.22 Hz), 8.27 (d, 1H, J=8.29 Hz), 8.03-8.05 (m, 1H), 7.73 (dd, 1H, J=8.06 Hz and 7.57 Hz), 7.56-7.65 (m, 3H), 7.37 (d, 1H, J=2.20 Hz), 7.15-7.18 (m, 1H), 4.40 (t, 2H, J=5.00 Hz), 3.53-3.59 (m, 1H), 3.39-3.49 (m, 1H), 3.21-3.25 (m, 1H), 3.10-3.20 (m, 1H), 2.81 (d, 3H, J=4.88 Hz), 1.21-1.25 ppm (m, 3H). Elemental Analysis for C22H23N3O3S.1.00 mol HCl.0.30 mol H2O:

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. dry with materialdried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography
  9. customDrying in vacuo at 69° C. for 20 minutes

Sources & evidence

ORD record
ord-fff3f200e4864472a540414f5626bdff
Source dataset
uspto-grants-2010_05
Patent number
US07723329B2

Reaction notes

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