Triethylamine → N-(6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl)pyrrolidine-1-carboxamide

HRID 2359692노트

반응식

HRID 2359692 반응식
[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH2:11])[CH:6]=1.[CH2:19]([N:21]([CH2:24][CH3:25])[CH2:22]C)[CH3:20].ClC(OC1C=CC=CC=1)=[O:28].N1CCCC1>O1CCCC1.[Cl-].[NH4+].ClCCl>[F:1][C:2]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[CH:13]=[CH:12][C:3]=1[O:4][C:5]1[N:10]=[CH:9][N:8]=[C:7]([NH:11][C:22]([N:21]2[CH2:24][CH2:25][CH2:20][CH2:19]2)=[O:28])[CH:6]=1

참가 물질

8

반응물 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 31268PyrrolidineHCID 231530124-Amino-6-(2-fluoro-4-nitrophenoxy)pyrimidine

생성물 1

HCID 57677447N-(6-(2-Fluoro-4-nitrophenoxy)pyrimidin-4-yl)pyrrolidine-1-carboxamide수율 43.2%

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 25517Ammonium Chloride용매

실험 절차

6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-amine (0.550 g, 2.2 mmol) was dissolved in tetrahydrofuran (10 ml). Then triethylamine (0.61 ml, 4.4 mmol) was added to the mixture with stirring. Then phenyl chloroformate (0.55 ml, 4.4 mmol) was added slowly to the mixture. The mixture was stirred at ambient temperature for 1.5 hours. Then pyrrolidine (1.8 ml, 22 mmol) was added to the mixture, and the mixture was stirred an additional 30 minutes. The mixture was diluted with sat ammonium chloride and dichloromethane and stirred an additional 10 minutes. The organic layer was collected by extracting with dichloromethane (3×10 ml). Combined organic layer was dried over sodium sulfate, filtered, and concentrated in-vacuo. The crude was purified by chromatography (Amino-Propyl silica gel column) in a gradient of 1-5% MeOH/dichloromethane to give an oil. The oil was recrystallized from dichloromethane/hexanes to give the desired product N-(6-(2-fluoro-4-nitrophenoxy)pyrimidin-4-yl)pyrrolidine-1-carboxamide (0.330 g, 0.95 mmol, 43% yield) as a yellow solid. MS (ESI pos. ion) m/z: 348 (MH+). Calc'd exact mass for C15H14FN5O4: 347. 1NMR (300 MHz, CDCl3): 1.94 (s, 4H), 3.37-3.49 (m, 4H), 5.23 (s, 1H), 7.09-7.21 (m, 1H), 7.29-7.38 (m, 1H), 7.99-8.09 (m, 2H), 8.25 (d, J=0.73 Hz, 1H).

후처리

  1. stirringThe mixture was stirred at ambient temperature for 1.5 hours
  2. stirringthe mixture was stirred an additional 30 minutes
  3. stirringstirred an additional 10 minutes
  4. customThe organic layer was collected
  5. extractionby extracting with dichloromethane (3×10 ml)
  6. dry with materialCombined organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in-vacuo
  9. customThe crude was purified by chromatography (Amino-Propyl silica gel column) in a gradient of 1-5% MeOH/dichloromethane
  10. customto give an oil
  11. customThe oil was recrystallized from dichloromethane/hexanes

출처 및 근거

ORD 기록
ord-e4cebf924b7c49c38e708a86e38974a9
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08685983B2

반응 노트

불러오는 중…