1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 66704943, 화합물

HRID 424759노트

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HRID 424759 반응식
Cl[C:2]1[N:11]=[C:10]2[C:5]([C:6](=[O:21])[C:7]([C:16]([O:18]CC)=[O:17])=[CH:8][N:9]2[C:12]([CH3:15])([CH3:14])[CH3:13])=[CH:4][C:3]=1[F:22].[CH:23]1([NH:26][CH2:27][C@@H:28]2[C@H:32]([F:33])[CH2:31][NH:30][CH2:29]2)[CH2:25][CH2:24]1.N12CCCN=C1CCCCC2>C(#N)C>[CH:23]1([NH:26][CH2:27][C@@H:28]2[C@H:32]([F:33])[CH2:31][N:30]([C:2]3[N:11]=[C:10]4[C:5]([C:6](=[O:21])[C:7]([C:16]([OH:18])=[O:17])=[CH:8][N:9]4[C:12]([CH3:13])([CH3:14])[CH3:15])=[CH:4][C:3]=3[F:22])[CH2:29]2)[CH2:25][CH2:24]1

참가 물질

5

반응물 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 11147857N-(((3R,4S)-4-Fluoropyrrolidin-3-yl)methyl)cyclopropanamineHCID 11844477HCID 11844477, 화합물

생성물 1

HCID 66704943HCID 66704943, 화합물수율 33.5%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
80 °C

실험 절차

Ethyl 7-chloro-6-fluoro-1,4-dihydro-1-(1,1-dimethylethyl)-4-oxo-1,8-naphthyridine-3-carboxylate (327 mg), (3R,4S)-3-cyclopropylaminomethyl-4-fluoropyrrolidine (174 mg), 1,8-diazabicyclo[5.4.0]undec-7-ene (160 mg) and acetonitrile (5 mL) were mixed together. The reaction mixture was stirred at 80° C. for 1 hour and was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (30 ml), washed sequentially with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:acetone=2:1->1:1->dichloromethane:methanol=10:1). The eluted pale yellow solid was dissolved in ethanol (4 mL), followed by addition of a 10% aqueous solution of sodium hydroxide (4 mL), stirring at 60° C. for 70 min, and concentration under reduced pressure. The resulting residue was diluted with water (10 mL), neutralized with 1 mol/L hydrochloric acid (pH 7.5), and extracted with dichloromethane (2×30 mL). The dichloromethane extracts were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:methanol=10:1) to give 7-[(3S,4S)-3-cyclopropylaminomethyl-4-fluoro-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-1-(1,1-dimethylethyl)-4-oxo-1,8-naphthyridine-3-carboxylic acid as white crystals (141 mg).

후처리

  1. concentrationwas concentrated under reduced pressure
  2. dissolutionThe resulting residue was dissolved in dichloromethane (30 ml)
  3. washwashed sequentially with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:acetone=2:1->1:1->dichloromethane:methanol=10:1)
  7. dissolutionThe eluted pale yellow solid was dissolved in ethanol (4 mL)
  8. additionfollowed by addition of a 10% aqueous solution of sodium hydroxide (4 mL)
  9. stirringstirring at 60° C. for 70 min
  10. concentrationconcentration under reduced pressure
  11. additionThe resulting residue was diluted with water (10 mL)
  12. extractionextracted with dichloromethane (2×30 mL)
  13. washwashed with saturated brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe resulting residue was purified by silica gel column chromatography (eluant: dichloromethane:methanol=10:1)

출처 및 근거

ORD 기록
ord-b79924730fe04d5f84c026f1e8a32040
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08106072B2

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