N-Methylethylamine → {2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl}-ethyl-methyl-amine

HRID 2240036Notes

Reaction equation

HRID 2240036 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:42]=[CH:43][CH:44]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH2:16][CH2:17]OS(C3C=CC(C)=CC=3)(=O)=O)=[CH:12][CH:13]=2)[C:8]([S:29]([C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:35]=[CH:34][CH:33]=2)(=[O:31])=[O:30])=[N:7]1.[CH2:45]([NH:47][CH3:48])[CH3:46]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:42]=[CH:43][CH:44]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH2:16][CH2:17][N:47]([CH2:45][CH3:46])[CH3:48])=[CH:12][CH:13]=2)[C:8]([S:29]([C:32]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[CH:35]=[CH:34][CH:33]=2)(=[O:31])=[O:30])=[N:7]1

Participants

4

Reactant 2

HCID 12219N-Methylethylamine2×HCID 58812063toluene-4-sulfonic acid 2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl ester

Product 1

HCID 58812143{2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl}-ethyl-methyl-amineYield 92.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A solution of toluene-4-sulfonic acid 2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl ester (0.350 g, 0.541 mmol) and ethylmethylamine (1.0 mL, 12 mmol) in THF (8 mL) was stirred for 2 hours in a sealed tube at 70° C. Additional ethylmethylamine (1.0 mL, 12 mmol) was added, and the reaction mixture was stirred at 80° C. in sealed tube for 2 hours. After cooling to ambient temperature, the reaction mixture was solvent evaporated and partitioned in ethyl acetate and aqueous sodium bicarbonate. The organic phase was then washed with brine, dried with anhydrous magnesium sulfate, filtered and concentrated. It was dried at 80° C. for 20 minutes in vacuo to yield {2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl}-ethyl-methyl-amine as a yellow semi-solid (0.268 g, 92.7%). This was dissolved in chloroform, and ethereal hydrochloride was added. The mixture was then concentrated and dried in vacuo at 82° C. for 14 hours. The result was the hydrochloride as a light orange foam (0.266 g); Mass Spectrum (+EI, [M+H]+) m/z 534. 1HNMR (500 MHz, DMSO-d6): δ9.90-9.93 (s, br, 1H), 8.73-8.75 (m, 1H), 8.54-8.57 (m, 1H), 8.27 (d, 1H, J=8.29 Hz), 8.02-8.05 (m, 1H), 7.82 (d, 1H, J=9.27 Hz), 7.70-7.74 (m, 1H), 7.56-7.63 (m, 2H), 7.30 (d. 1H, J=2.20 Hz), 7.15-7.26 (m, 4H), 7.04 (d, 1H, J=7.57 Hz), 5.73 (s, 2H), 4.36-4.38 (m, 2H), 3.40-3.55 (m, 3H), 3.09-3.14 (br, 1H), 2.78 (s, 3H), 1.19-1.23 ppm (m, 3H). Elemental Analysis for C29H28ClN3O3S.1.00 HCl.0.75 mol H2O: Calcd: C, 59.64; H, 5.26; N, 7.19; Found: C, 59.24; H, 5.17; N, 6.89.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customevaporated
  3. custompartitioned in ethyl acetate
  4. washThe organic phase was then washed with brine
  5. dry with materialdried with anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customIt was dried at 80° C. for 20 minutes in vacuo

Sources & evidence

ORD record
ord-db3324804b0749b9b1170856a20c3f07
Source dataset
uspto-grants-2010_05
Patent number
US07723329B2

Reaction notes

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