Hydrochloric Acid → 2-[4-(benzyloxy)phenyl]-N-[3-bromo-1-(2-pyrrolidin-1-ylethyl)-1H-indazol-4-yl]acetamide

HRID 1790161Notes

Reaction equation

HRID 1790161 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([NH:18][C:19]2[CH:27]=[CH:26][CH:25]=[C:24]3[C:20]=2[CH:21]=[N:22][N:23]3[CH2:28][CH2:29][N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:17])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[Br-:37].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.Cl>O.CO>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([NH:18][C:19]2[CH:27]=[CH:26][CH:25]=[C:24]3[C:20]=2[C:21]([Br:37])=[N:22][N:23]3[CH2:28][CH2:29][N:30]2[CH2:31][CH2:32][CH2:33][CH2:34]2)=[O:17])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 114196662-[4-(benzyloxy)phenyl]-N-[1-(2-pyrrolidin-1-ylethyl)-1H-indazol-4-yl]acetamideHCID 21124087Pyridiniumtribromide

Product 1

HCID 117207372-[4-(benzyloxy)phenyl]-N-[3-bromo-1-(2-pyrrolidin-1-ylethyl)-1H-indazol-4-yl]acetamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-[4-(benzyloxy)phenyl]-N-[1-(2-pyrrolidin-1-ylethyl)-1H-indazol-4-yl]acetamide (Example 3, 0.200 g, 0.440 mmol) and NaOH (0.400 g, 10.0 mmol) in H2O (6 mL) was added in methanol (6 mL) was placed in an ice-water bath for 15 minutes before pyridinium tribromide (0.470 g, 1.47 mmol) in MeOH (1.5 mL) was added. The reaction mixture was stirred at 0° C. for 5 hours after which the pH was adjusted to 7 with diluted HCl. The mixture was extracted with ethyl acetate, and the combined organic layer washed with H2O and concentrated under reduced pressure. The residue was purified by flash chromatography to provide the title compound. 1H NMR (300 MHz, DMSO-d6) ppm 1.60 (m, 4H), 2.43 (m, 4H), 2.85 (t, 2H, J=6.44), 3.68 (s, 2H), 4.48 (t, 2H, J=6.44), 5.10 (s, 2H), 7.00 (d, 2H, J=8.47), 7.29–7.48 (m, 7H), 7.55 (s, 2H), 7.64 (s, 1H), 10.05 (s, 1H); MS (DCI/NH3) m/z 533 [M+H]+.

Workup

  1. additionwas added
  2. extractionThe mixture was extracted with ethyl acetate
  3. washthe combined organic layer washed with H2O
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-c6bb2a64285e402fb31d762dc9f96674
Source dataset
uspto-grants-2006_07
Patent number
US07071182B2

Reaction notes

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