Trifluoroacetic acid → 2-(2-(2-(2-((4-(Piperidin-4-yl)-2-(trifluoromethoxy)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide

HRID 2272438ノート

反応式

HRID 2272438 の反応式
[NH2:1][C:2](=[O:47])[CH2:3][C:4]1[CH:46]=[CH:45][CH:44]=[CH:43][C:5]=1[CH2:6][CH2:7][C:8]1[C:13]([C:14]([F:17])([F:16])[F:15])=[CH:12][N:11]=[C:10]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH:25]3[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]3)=[CH:21][C:20]=2[O:38][C:39]([F:42])([F:41])[F:40])[N:9]=1.FC(F)(F)C(O)=O>C(Cl)Cl.CCOC(C)=O.CO>[NH3:1].[NH:28]1[CH2:29][CH2:30][CH:25]([C:22]2[CH:23]=[CH:24][C:19]([NH:18][C:10]3[N:9]=[C:8]([CH2:7][CH2:6][C:5]4[CH:43]=[CH:44][CH:45]=[CH:46][C:4]=4[CH2:3][C:2]([NH2:1])=[O:47])[C:13]([C:14]([F:16])([F:17])[F:15])=[CH:12][N:11]=3)=[C:20]([O:38][C:39]([F:41])([F:40])[F:42])[CH:21]=2)[CH2:26][CH2:27]1

参加物

7

反応物 2

HCID 6422Trifluoroacetic acidHCID 86675847tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylate

生成物 2

HCID 222Ammonia収率 1%HCID 866758482-(2-(2-(2-((4-(Piperidin-4-yl)-2-(trifluoromethoxy)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)acetamide収率 159.2%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒2 回HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3-(trifluoromethoxy)phenyl)piperidine-1-carboxylate (I50) (0.062 g, 0.093 mmol) was dissolved in dry DCM (6 mL) under an atmosphere of nitrogen. Trifluoroacetic acid (0.142 mL, 1.86 mmol) was added to the solution and the reaction was stirred at room temperature for 20 hours. Volatiles were removed in vacuo, EtOAc (50 mL) and 2 M aq. NaOH (50 mL) were added to the residue and the layers were separated. The aqueous layer was extracted with EtOAc (2×70 mL), the combined organics were washed with water (50 mL), brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo to give an off-white solid. The crude material was purified by silica gel chromatography (12 g Si Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., then 0-100% methanol in EtOAc, then 1% ammonia in methanol), to give the title compound (10) (0.042 g, 80% yield) as a white solid; 1H NMR (400 MHz, d6-DMSO) δ 9.78 (s, 1H), 8.59 (s, 1H), 7.59 (d, J=8.3 Hz, 1H), 7.39 (s, 1H), 7.29-7.17 (m, 3H), 7.18-7.06 (m, 3H), 6.90 (s, 1H), 3.45 (s, 2H), 3.09-2.92 (m, 6H), 2.71-2.53 (m, 3H), 1.71 (d, J=11.7 Hz, 2H), 1.49 (qd, J=12.1, 3.7 Hz, 2H). LCMS Method C: rt 5.07 min; m/z 568.1[M+H]+.

後処理

  1. customVolatiles were removed in vacuo, EtOAc (50 mL) and 2 M aq. NaOH (50 mL)
  2. additionwere added to the residue
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc (2×70 mL)
  5. washthe combined organics were washed with water (50 mL), brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give an off-white solid
  10. customThe crude material was purified by silica gel chromatography (12 g Si Cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

出典と根拠

ORDレコード
ord-df6e5d059704433b8e346723c9ef2c77
出典データセット
uspto-grants-2015_09
特許番号
US09120761B2

反応ノート

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