Tetrahydrofuran → cis-3-(4-Amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane

HRID 2288762노트

반응식

HRID 2288762 반응식
C([N:8]1[CH2:15][C@@H:14]2[C@@H:10]([CH2:11][N:12]([C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][C:17]=3[F:25])[CH2:13]2)[CH2:9]1)C1C=CC=CC=1.C1COCC1.C([O-])=O.[NH4+]>[Pd].CO>[NH2:22][C:19]1[CH:20]=[CH:21][C:16]([N:12]2[CH2:11][C@@H:10]3[C@@H:14]([CH2:15][NH:8][CH2:9]3)[CH2:13]2)=[C:17]([F:25])[CH:18]=1

참가 물질

6

반응물 3

HCID 8028TetrahydrofuranHCID 2723923Ammonium formateHCID 21969626cis-3-Benzyl-7-(2-fluoro-4-nitrophenyl)-3,7-diazabicyclo[3,3,0]octane

생성물 1

HCID 70202150cis-3-(4-Amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 887Methanol용매

실험 절차

cis-3-Benzyl-7-(2-fluoro-4-nitrophenyl)-3,7-diazabicyclo[3.3.0]octane (9.11 g, 26.71 mmol), THF (100 mL), and methanol (50 mL) are combined with 10% palladium on carbon (6.67 g) and ammonium formate (16.83 g, 266.90 mmol) under nitrogen, heated to reflux for 2.5 hours, cooled to ambient temperature, stirred 15 hours, filtered through celite and concentrated in vacuo to give crude cis-3-(4-amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane. cis-3-(4-Amino-2-fluorophenyl]-3,7-diazabicyclo[3.3.0]octane, water (100 mL), acetone (100 mL), and potassium carbonate (7.75 g, 56.07 mmol) are combined, cooled to 0° C., and benzyl chloroformate is added slowly. The reaction is warmed to ambient temperature, stirred 15 hours, concentrated in vacuo, and diluted with ethyl acetate. The organic phase is washed with water (2×150 mL) and saline (150 mL), dried over sodium sulfate, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 100 mL), eluting with hexane/ethyl acetate (80/20). The appropriate fractions are combined (Rf =0.41, TLC, hexane/ethyl acetate, 50/50) and concentrated in vacuo to give the title compound, mp 121-122° C.

후처리

  1. temperatureheated
  2. temperatureto reflux for 2.5 hours
  3. filtrationfiltered through celite and
  4. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-cc8398273f7c47ee850ce4b94eaef61a
출처 데이터셋
uspto-grants-2000_07
특허 번호
US06090820

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