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

HRID 886710Notes

Reaction equation

HRID 886710 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].N1C=CC=CC=1.[C:32]1([CH3:42])[CH:37]=[CH:36][C:35]([S:38](Cl)(=[O:40])=[O:39])=[CH:34][CH:33]=1>ClCCl>[CH3:42][C:32]1[CH:37]=[CH:36][C:35]([S:38]([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:40])=[O:39])=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 73974-Toluenesulfonyl chloride3×HCID 59487493(S)-5-Amino-1-(4-fluorophenyl)-N-[3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)propyl]-1H-pyrazole-4-carboxamide

Product 1

HCID 59487499(S)-2-[({[5-Amino-1-(4-fluorophenyl)-1H-pyrazol-4-yl]carbonyl}amino)methyl]-3,3,3-trifluoro-2-hydroxypropyl 4-methylbenzenesulfonateYield 73.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

(S)-5-Amino-1-(4-fluorophenyl)-N-[3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)propyl]-1H-pyrazole-4-carboxamide (90 mg) was dissolved in dry dichloromethane (3 ml) and dry pyridine (3 ml) and cooled in an ice bath under nitrogen. p-Toluenesulphonyl chloride (62 mg) was added and the reaction was stirred at ice bath temperature for 1 hour and then at room temperature for 24 hours. p-Toluenesulphonyl chloride (25 mg) was added and the reaction was stirred at room temperature, under nitrogen over the weekend. p-Toluenesulphonyl chloride (25 mg) was added and the reaction was stirred at room temperature under nitrogen for 2 hours and heated at 50° C. for 2 hours and left stirring at room temperature overnight. The solvent was evaporated and the residue was partitioned between dichloromethane and water. The organic layer was washed with 1M hydrochloric acid, water, sodium bicarbonate and brine, dried using a hydrophobic frit and evaporated to give a beige foam (94 mg). This was dissolved in dichloromethane and applied to a 10 g SPE cartridge and purified on the Flashmaster eluting with a 0-50% ethyl acetate in cyclohexane over a 20 minute gradient. The appropriate fraction was evaporated to give the title compound as a colourless oil (83 mg).

Workup

  1. waitat room temperature for 24 hours
  2. stirringthe reaction was stirred at room temperature, under nitrogen over the weekend
  3. stirringthe reaction was stirred at room temperature under nitrogen for 2 hours
  4. waitleft
  5. stirringstirring at room temperature overnight
  6. customThe solvent was evaporated
  7. customthe residue was partitioned between dichloromethane and water
  8. washThe organic layer was washed with 1M hydrochloric acid, water, sodium bicarbonate and brine
  9. customdried
  10. customevaporated

Sources & evidence

ORD record
ord-ace6ad2c4fb746a4b3b74483e31ad112
Source dataset
uspto-grants-2012_08
Patent number
US08247377B2

Reaction notes

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