Diisopropylethylamine → 5-Amino-N-[2-({[(2-chloro-6-fluorophenyl)carbonyl]amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

HRID 886723

반응식

HRID 886723 반응식
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](Cl)=[O:5].[NH2:12][C:13]1[N:17]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[N:16]=[CH:15][C:14]=1[C:25]([NH:27][CH2:28][C:29]([CH2:35][NH2:36])([OH:34])[C:30]([F:33])([F:32])[F:31])=[O:26].C(N(C(C)C)CC)(C)C>O1CCCC1.ClCCl>[NH2:12][C:13]1[N:17]([C:18]2[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=2)[N:16]=[CH:15][C:14]=1[C:25]([NH:27][CH2:28][C:29]([CH2:35][NH:36][C:4]([C:3]1[C:7]([F:11])=[CH:8][CH:9]=[CH:10][C:2]=1[Cl:1])=[O:5])([OH:34])[C:30]([F:33])([F:32])[F:31])=[O:26]

참가 물질

6

반응물 3

HCID 81531DiisopropylethylamineHCID 27365472-Chloro-6-fluorobenzoyl chlorideHCID 594874945-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide

생성물 1

HCID 248097125-Amino-N-[2-({[(2-chloro-6-fluorophenyl)carbonyl]amino}methyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide수율 98.7%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

실험 절차

A solution of 2-chloro-6-fluorobenzoyl chloride (0.169 g) in dry tetrahydrofuran (1 ml) was added to a stirred mixture of 5-amino-N-[2-(aminomethyl)-3,3,3-trifluoro-2-hydroxypropyl]-1-(4-fluorophenyl)-1H-pyrazole-4-carboxamide (0.289 g) and diisopropylethylamine (0.21 ml) in a mixture of dichloromethane (4 ml) and tetrahydrofuran (3 ml) cooled to <5° C. After the addition, the cooling bath was removed and the reaction mixture stirred at room temperature for 20 minutes. Water (10 ml) and dichloromethane (10 ml) were added to the reaction mixture and the resultant mixture stirred vigorously. The phases were separated using a hydrophobic frit and the aqueous phase washed with additional dichloromethane (10 ml). The organic phase was evaporated and the residue purified by chromatography on silica (20 g cartridge) eluting with 0-100% ethyl acetate in cyclohexane. Appropriate fractions were combined and evaporated to give the title compound (0.409 g).

후처리

  1. temperaturecooled to <5° C
  2. additionAfter the addition
  3. customthe cooling bath was removed
  4. additionWater (10 ml) and dichloromethane (10 ml) were added to the reaction mixture
  5. stirringthe resultant mixture stirred vigorously
  6. customThe phases were separated
  7. washthe aqueous phase washed with additional dichloromethane (10 ml)
  8. customThe organic phase was evaporated
  9. customthe residue purified by chromatography on silica (20 g cartridge)
  10. washeluting with 0-100% ethyl acetate in cyclohexane
  11. customevaporated

출처 및 근거

ORD 기록
ord-130f634af29742388a74cb5c5e10ea21
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08247377B2

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