tert-Butyl 4-(4-((4-((3-(methoxycarbonyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate → tert-Butyl 4-(4-((4-(3-(methoxycarbonyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate

HRID 1473046ノート

反応式

HRID 1473046 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:11]#[C:12][C:13]2[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]3[CH:29]=[CH:28][C:27]([N:30]4[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]4)=[CH:26][CH:25]=3)[N:14]=2)[CH:8]=[CH:9][CH:10]=1)=[O:4].[H][H]>CN(C=O)C.CCOC(C)=O.[Pd]>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:8]=[CH:9][CH:10]=1)[CH2:11][CH2:12][C:13]1[C:18]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]2[CH:25]=[CH:26][C:27]([N:30]3[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])[CH2:34][CH2:35]3)=[CH:28][CH:29]=2)[N:14]=1)=[O:4]

参加物

6

反応物 2

HCID 71229923tert-Butyl 4-(4-((4-((3-(methoxycarbonyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylateHCID 178418361HCID 178418361、化合物

生成物 1

HCID 68283092tert-Butyl 4-(4-((4-(3-(methoxycarbonyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate収率 66.3%

試薬・触媒・溶媒 3

HCID 23938Palladium触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

tert-Butyl 4-(4-((4-((3-(methoxycarbonyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I32) (0.180 g, 0.309 mmol) was dissolved in dry DMF (10 mL) under an atmosphere of nitrogen. 10% Pd/C (0.100 g) in EtOAc (10 mL) was added to the solution and the atmosphere was changed to hydrogen gas (balloon). The reaction was sealed with a balloon and stirred at room temperature for 18 hours after which the reaction was flushed with nitrogen gas and Pearlman's catalyst (0.150 g) in EtOAc (5 mL) was added. The atmosphere was again changed to hydrogen gas (balloon) and the reaction was sealed with balloon and stirred for 20 hours at room temperature. The catalyst was removed by filtration through Celite, which was washed with EtOAc (5×10 mL). The solvent was removed in vacuo to give a yellow oil which was purified by silica gel chromatography (Biotage Isolera, 40 g Si Cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.) to give the title compound (I33) (0.120 g, 66% yield) as a yellow foam; 1H NMR (400 MHz, d6-DMSO) δ 10.01 (s, 1H), 8.60 (s, 1H), 7.88-7.77 (m, 2H), 7.61-7.39 (m, 4H), 6.93 (d, J=9.1 Hz, 2H), 3.85 (s, 3H), 3.52-3.42 (m, 4H), 3.21-2.99 (m, 8H), 1.42 (s, 9H). LCMS Method C: rt 6.86 min; m/z 586.3 [M+H]+.

後処理

  1. customThe reaction was sealed with a balloon
  2. customwas flushed with nitrogen gas and Pearlman's catalyst (0.150 g) in EtOAc (5 mL)
  3. additionwas added
  4. customthe reaction was sealed with balloon
  5. stirringstirred for 20 hours at room temperature
  6. customThe catalyst was removed by filtration through Celite, which
  7. washwas washed with EtOAc (5×10 mL)
  8. customThe solvent was removed in vacuo
  9. customto give a yellow oil which
  10. customwas purified by silica gel chromatography (Biotage Isolera, 40 g Si Cartridge, 0-40% EtOAc in petroleum benzine 40-60° C.)

出典と根拠

ORDレコード
ord-4b4afd56bfd64c0abfe8afc5e3cbde97
出典データセット
uspto-grants-2015_04
特許番号
US09012461B2

反応ノート

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