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

HRID 886710노트

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HRID 886710 반응식
[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

참가 물질

5

반응물 3

HCID 1049PyridineHCID 73974-Toluenesulfonyl chloride3회HCID 59487493(S)-5-Amino-1-(4-fluorophenyl)-N-[3,3,3-trifluoro-2-hydroxy-2-(hydroxymethyl)propyl]-1H-pyrazole-4-carboxamide

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
50 °C

실험 절차

(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).

후처리

  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

출처 및 근거

ORD 기록
ord-ace6ad2c4fb746a4b3b74483e31ad112
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08247377B2

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