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

反応式

HRID 886723 の反応式
[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]

参加物

6

反応物 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

生成物 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-carboxamide収率 98.7%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-130f634af29742388a74cb5c5e10ea21
出典データセット
uspto-grants-2012_08
特許番号
US08247377B2

関連ノート

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