4-Toluenesulfonyl chloride → 2-[({[5-Amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]carbonyl}amino)methyl]-3,3,3-trifluoro-2-hydroxypropyl 4-methylbenzenesulfonate

HRID 886698Notes

Reaction equation

HRID 886698 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14]([NH:16][CH2:17][C:18]([OH:25])([CH2:23][OH:24])[C:19]([F:22])([F:21])[F:20])=[O:15].[C:26]1([CH3:36])[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1>ClCCl.N1C=CC=CC=1>[CH3:36][C:26]1[CH:31]=[CH:30][C:29]([S:32]([O:24][CH2:23][C:18]([CH2:17][NH:16][C:14]([C:3]2[CH:4]=[N:5][N:6]([C:7]3[CH:8]=[CH:9][C:10]([F:13])=[CH:11][CH:12]=3)[C:2]=2[NH2:1])=[O:15])([OH:25])[C:19]([F:22])([F:21])[F:20])(=[O:34])=[O:33])=[CH:28][CH:27]=1

Participants

5

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 591872265-amino-1-(4-fluorophenyl)-N-[3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)propyl]-1H-pyrazole-4-carboxamide

Product 1

HCID 591872402-[({[5-Amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]carbonyl}amino)methyl]-3,3,3-trifluoro-2-hydroxypropyl 4-methylbenzenesulfonateYield 97.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 5-amino-1-(4-fluorophenyl)-N-[3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)propyl]-1H-pyrazole-4-carboxamide (2.47 g, 6.82 mmol) in anhydrous dichloromethane (20 ml) and anhydrous pyridine (20 ml) cooled in an ice bath under a nitrogen atmosphere was added p-toluenesulphonyl chloride (1.7 g, 8.9 mmol). The mixture was stirred for 6 hours at ice bath temperature before being allowed to warm to room temperature and stirred overnight. The solution was evaporated under vacuum and the residue was partitioned between ethyl acetate (100 ml) and water (30 ml). The separated organic phase was washed with 2M hydrochloric acid (2×30 ml), water (30 ml), saturated sodium hydrogen carbonate (30 ml), water (30 ml) and saturated brine (50 ml) before being dried over sodium sulphate and evaporated under reduced pressure to give a foam (3.45 g). This foam was purified on a Flashmaster column of Silica (100 g) using a 0-100% ethyl acetate in cyclohexane gradient over 1 hour. This afforded the title compound (2.8 g, 79%) as a foam.

Workup

  1. stirringstirred overnight
  2. customThe solution was evaporated under vacuum
  3. customthe residue was partitioned between ethyl acetate (100 ml) and water (30 ml)
  4. washThe separated organic phase was washed with 2M hydrochloric acid (2×30 ml), water (30 ml), saturated sodium hydrogen carbonate (30 ml), water (30 ml) and saturated brine (50 ml)
  5. dry with materialbefore being dried over sodium sulphate
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-53241be3f3cf429b8aa6350c1ac66f34
Source dataset
uspto-grants-2012_08
Patent number
US08247377B2

Reaction notes

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