Benzophenone imine → (S)-tert-butyl 3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate

HRID 516187노트

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HRID 516187 반응식
Cl[C:2]1[C:7]2[C:8]([C:23]#[C:24][C:25]3[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[C:27]([O:33][CH3:34])[CH:26]=3)=[CH:9][N:10]([C@H:11]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]3)[C:6]=2[CH:5]=[CH:4][N:3]=1.CC(C)([O-])C.[Na+].C(=[NH:54])(C1C=CC=CC=1)C1C=CC=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:54][C:2]1[C:7]2[C:8]([C:23]#[C:24][C:25]3[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=[C:27]([O:33][CH3:34])[CH:26]=3)=[CH:9][N:10]([C@H:11]3[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]3)[C:6]=2[CH:5]=[CH:4][N:3]=1

참가 물질

6

반응물 3

HCID 136809Benzophenone imineHCID 23676156Sodium t-butoxideHCID 89870976(S)-tert-butyl 3-(4-chloro-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate

생성물 1

HCID 89871097(S)-tert-butyl 3-(4-amino-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

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온도
115 °C

실험 절차

Under a nitrogen atmosphere, the (S)-tert-butyl 3-(4-chloro-3-((3,5-dimethoxyphenyl)ethynyl)-1H-pyrrolo[3,2-c]pyridin-1-yl)pyrrolidine-1-carboxylate (120 mg) obtained in Step 3,2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (BINAP) (26 mg), sodium tert-butoxide (72 mg), benzophenone imine (92 mg), and tris(dibenzylideneacetone)dipalladium (36 mg) were suspended in toluene (10 ml), and the result was stirred at 115° C. for 90 minutes. After dilution with ethyl acetate, celite filtration was performed. The solvent was distilled off under reduced pressure. Hydroxyaminehydrochloride (366 mg), sodium bicarbonate (442 mg), methanol (16 ml), and water (4 ml) were added to the resulting residue, and the resulting mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure. Thereafter, ethyl acetate and a saturated sodium chloride solution were added to separate the organic layer. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate) to obtain the title compound as a colorless, amorphous substance (35 mg). Physical properties: m/z [M+H]+ 463.4

후처리

  1. filtrationAfter dilution with ethyl acetate, celite filtration
  2. distillationThe solvent was distilled off under reduced pressure
  3. additionHydroxyaminehydrochloride (366 mg), sodium bicarbonate (442 mg), methanol (16 ml), and water (4 ml) were added to the resulting residue
  4. stirringthe resulting mixture was stirred at room temperature for 2 hours
  5. distillationThe solvent was distilled off under reduced pressure
  6. additionThereafter, ethyl acetate and a saturated sodium chloride solution were added
  7. customto separate the organic layer
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. distillationthe solvent was distilled off under reduced pressure
  10. customThe resulting residue was purified by basic silica gel column chromatography (developing solvent: hexane/ethyl acetate)

출처 및 근거

ORD 기록
ord-a3a30776979f43da93bcc36f64575c62
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108973B2

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