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

HRID 2240038Notes

Reaction equation

HRID 2240038 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](=CC=CC=3)[CH:35]=[CH:34][CH:33]=2)(=[O:31])=[O:30])=[N:7]1.[CH:45]([NH2:48])([CH3:47])[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][NH:48][CH:45]([CH3:47])[CH3:46])=[CH:12][CH:13]=2)[C:8]([S:29]([C:32]2[C:41]3[C:36](=[CH:3][CH:2]=[CH:44][CH:43]=3)[CH:35]=[CH:34][CH:33]=2)(=[O:30])=[O:31])=[N:7]1

Participants

4

Reactant 2

HCID 6363Isopropylamine3×HCID 58812063toluene-4-sulfonic acid 2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl ester

Product 1

HCID 58812099{2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl}-isopropyl-amineYield 200.1%

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 (0.339 g, 0.524 mmol) and isopropylamine (1.0 mL, 12 mmol) in THF (8 mL) was stirred at 70° C. in a sealed tube for 2 hours. Isopropylamine (1.0 mL, 12 mmol) was added, and the reaction mixture was stirred at 80° C. in a sealed tube for 2 hours. Isopropylamine (1.0 mL, 12 mmol) was added to the reaction mixture, and it was stirred at 80° C. in a sealed tube for 30 hours. After cooling to ambient temperature, the reaction mixture was solvent evaporated and partitioned in ethyl acetate and aqueous sodium bicarbonate. It was washed with brine, dried with anhydrous magnesium sulfate, filtered, concentrated and dried in vacuo for 20 minutes at 80° C. to give {2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl}-isopropyl-amine as a yellow solid (0.280 g, 100%). It was dissolved in chloroform, and ethereal hydrochloride was added. The resulting solid was filtered and dried at 82° C. in vacuo for 14 hours. The result was the hydrochloride as a pale yellow solid (0.236 g): MP: 206-8° C.; Mass Spectrum (+EI, [M+H]+) m/z 534. 1HNMR (500 MHz, DMSO-d6): δ8.65-8.76 (m, 3H), 8.54-8.56 (m, 1H), 8.27 (d, 1H, J=8.17 Hz), 8.02-8.05 (m, 1H), 7.82 (d, 1H, J=9.27 Hz), 7.72 (dd, 1H, J=8.07 Hz and 7.57 Hz), 7.57-7.63 (m, 2H), 7.24-7.28 (m, 2H), 7.16-7.21 (m, 3H), 7.05 (d, 1H, J=7.81 Hz), 5.73 (s, 2H), 4.27 (t, 2H, J=5.00 Hz), 3.31-3.37 (m, 3H), 1.23 ppm (d, 6H, J=6.69 Hz). Elemental Analysis for C29H28ClN3O3S.1.00 HCl: Calcd: C, 61.05; H, 5.12; N, 7.36; Found: C, 60.68; H, 5.26; N, 7.14.

Workup

  1. stirringwas stirred at 80° C. in a sealed tube for 30 hours
  2. temperatureAfter cooling to ambient temperature
  3. customevaporated
  4. custompartitioned in ethyl acetate
  5. washIt was washed with brine
  6. dry with materialdried with anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customdried in vacuo for 20 minutes at 80° C.

Sources & evidence

ORD record
ord-77dc35b72f56419995e5583a1b285c95
Source dataset
uspto-grants-2010_05
Patent number
US07723329B2

Reaction notes

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