4-Toluenesulfonyl chloride → HCID 71240690, compound

HRID 80742Notes

Reaction equation

HRID 80742 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:12]([CH3:13])=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6]([CH3:14])=[N:7][NH:8]2.[S:15](Cl)([C:18]1[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=1)(=[O:17])=[O:16].[NH4+].[Cl-]>C1COCC1>[Cl:3][C:4]1[C:12]([CH3:13])=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6]([CH3:14])=[N:7][N:8]2[S:15]([C:18]1[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=1)(=[O:17])=[O:16]

Participants

6

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 178423509HCID 178423509, compound

Product 1

HCID 71240690HCID 71240690, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 1-(2-chloro-6-fluoro-3-methylphenyl)ethanone (10 g, 53.6 mmol) and hydrazine (5.05 mL, 161 mmol) in DMSO (50 mL) was heated at 80° C. overnight. The reaction mixture was then partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated to provide crude 4-chloro-3,5-dimethyl-1H-indazole as a white solid, which was used in the next step directly. MS (ESI+) m/z 180.9 (M+H)+. NaH (60% dispersion in mineral oil, 3.87 g, 97 mmol) was added portion wise to a solution of crude 4-chloro-3,5-dimethyl-1H-indazole (9.7 g, 53.7 mmol) in THF (200 mL) at −20° C. The mixture was allowed to warm to 0° C. and stir for 20 min, then TsCl (14.33 g, 75 mmol) was added. The reaction mixture was allowed to warm to rt and stir overnight. The reaction mixture was cooled to −20° C. and sat. NH4Cl aqueous solution was added to quench excess base. The resulting mixture was extracted with CH2Cl2 (2×). The combined organics were washed with brine, dried (Na2SO4) and concentrated. The residue was triturated with EtOAc and filtered to provide 4-chloro-3,5-dimethyl-1-tosyl-1H-indazole. 1H NMR (400 MHz, CDCl3) δ ppm 7.98 (d, J=8.34 Hz, 1 H) 7.84 (m, J=8.34 Hz, 2 H) 7.39 (d, J=8.59 Hz, 1 H) 7.25 (m, J=7.83 Hz, 2 H) 2.73 (s, 3 H) 2.46 (s, 3 H) 2.38 (s, 3 H); MS (ESI+) m/z 334.7 (M+H)+.

Workup

  1. temperatureto warm to rt
  2. stirringstir overnight
  3. temperatureThe reaction mixture was cooled to −20° C.
  4. customto quench excess base
  5. extractionThe resulting mixture was extracted with CH2Cl2 (2×)
  6. washThe combined organics were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was triturated with EtOAc
  10. filtrationfiltered

Sources & evidence

ORD record
ord-d6f4c828e7424b0e85a8915cbbbe903e
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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