Pyrrolidine → 1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-5-(2-pyrrolidin-1-yl-ethoxy)-1H-indazole

HRID 2240039Notes

Reaction equation

HRID 2240039 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.[NH:45]1[CH2:49][CH2:48][CH2:47][CH2:46]1>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:45]3[CH2:49][CH2:48][CH2:47][CH2:46]3)=[CH:12][CH:13]=2)[C:8]([S:29]([C:32]2[C:41]3[C:40](=[CH:39][CH:38]=[CH:37][CH:36]=3)[CH:35]=[CH:34][CH:33]=2)(=[O:30])=[O:31])=[N:7]1

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 58812063toluene-4-sulfonic acid 2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl ester

Product 1

HCID 588121141-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-5-(2-pyrrolidin-1-yl-ethoxy)-1H-indazoleYield 87.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of toluene-4-sulfonic acid 2-[1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-1H-indazol-5-yloxy]-ethyl ester (0.359 g, 0.555 mmol) and pyrrolidine (1.0 mL, 12 mmol) in THF (8 mL) was stirred at 70° C. in a sealed tube for 2 hours. After cooling to ambient temperature, the reaction mixture was solvent evaporated. It was then partitioned in ethyl acetate and aqueous sodium bicarbonate. The organic phase was washed with brine, dried with anhydrous magnesium sulfate, filtered, concentrated and dried in vacuo at 80° C. for 20 minutes to give 1-(3-chloro-benzyl)-3-(naphthalene-1-sulfonyl)-5-(2-pyrrolidin-1-yl-ethoxy)-1H-indazole as a yellow semi-solid (0.266 g, 87.8%). This was dissolved in chloroform, and ethereal hydrochloride was added. The mixture was concentrated and dried at 82° C. in vacuo for 14 hours to yield the hydrochloride as a light orange foam (0.205 g); Mass Spectrum (+EI, [M+H]+) m/z 546. 1HNMR (500 MHz, DMSO-d6): δ10.18-10.19 (s, 1H), 8.73-8.75 (m, 1H), 8.55-8.57 (m, 1H), 8.27 (d, 1H, J=8.30 Hz), 8.02-8.04 (m, 1H), 7.82 (d, 1H, J=9.15 Hz), 7.70-7.74 (m, 1H), 7.57-7.64 (m, 2H), 7.15-7.29 (m, 5H), 7.04 (d, 1H, J=7.69 Hz), 5.73 (s, 2H), 4.33-4.35 (m, 2H), 3.55 (br, s, 4H), 3.07-3.15 (s, br, 2H), 1.81-2.02 ppm (br, m, 4H). Elemental Analysis for C30H28ClN3O3S.1.00 HCl.0.70 mole H2O: Calcd: C, 60.54; H, 5.15; N, 7.06; Found: C, 60.16; H, 5.11; N, 6.74.

Workup

  1. customevaporated
  2. customIt was then partitioned in ethyl acetate
  3. washThe organic phase was washed with brine
  4. dry with materialdried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customdried in vacuo at 80° C. for 20 minutes

Sources & evidence

ORD record
ord-0ba6ac8965d3487596cc563efe980402
Source dataset
uspto-grants-2010_05
Patent number
US07723329B2

Reaction notes

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