Hydrochloric Acid → 5-[4-(4-Fluoro-phenyl)-3-hydroxy-butyl]-1-[6-(2H-tetrazol-5-yl)-hexyl]-pyrrolidin-2-one

HRID 1582661노트

반응식

HRID 1582661 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([OH:26])[CH2:10][CH2:11][CH:12]2[CH2:16][CH2:15][C:14](=[O:17])[N:13]2[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]#[N:25])=[CH:4][CH:3]=1.[N:27]([Si](C)(C)C)=[N+:28]=[N-:29].C([Sn](=O)CCCC)CCC.Cl>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH:9]([OH:26])[CH2:10][CH2:11][CH:12]2[N:13]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]3[N:27]=[N:28][NH:29][N:25]=3)[C:14](=[O:17])[CH2:15][CH2:16]2)=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 313Hydrochloric AcidHCID 61221Dibutyltin oxide2회HCID 78378Azidotrimethylsilane2회HCID 227187637-{2-[4-(4-Fluoro-phenyl)-3-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}heptanenitrile

생성물 1

HCID 101267755-[4-(4-Fluoro-phenyl)-3-hydroxy-butyl]-1-[6-(2H-tetrazol-5-yl)-hexyl]-pyrrolidin-2-one수율 49.1%

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

Following the procedure described for Example 3, Step D, 7-{2-[4-(4-fluoro-phenyl)-3-hydroxy-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrile (71 mg, 0.197 mmol) was reacted with azidotrimethylsilane (45 mg, 0.394 mmol) and dibutyltin oxide (5 mg, 0.02 mmol) in toluene (10 mL) heated under reflux for 16 h. Additional azidotrimethylsilane (200 mg) and dibutyltin oxide (50 mg) were added and the reaction mixture was heated under reflux for 5 h. The reaction mixture was acidified with 1N HCl to pH=2 (5 mL) and the aqueous solution was washed with EtOAc (4×10 mL). The combined organic solutions were dried (MgSO4), filtered, and concentrated. Purification by medium pressure chromatography (EtOAc to 39:1 EtOAc:MeOH to 19:1 EtOAc:MeOH) provided the title compound of Example 5A (39 mg). 1H NMR (CDCl3) δ7.16 (m, 2H), 7.00 (m, 2H), 3.81 (m, 1H), 3.68 (m, 1H), 3.53 (m, 1H), 2.99 (m, 3H), 2.80 (m, 1H), 2.68 (m, 1H), 2.47 (m, 2H), 2.20 (m, 1H), 1.88-1.22 (m, 14H); MS 404.3 (M+1); 402.3 (M−1).

후처리

  1. temperatureheated
  2. temperatureunder reflux for 16 h
  3. temperaturethe reaction mixture was heated
  4. temperatureunder reflux for 5 h
  5. washthe aqueous solution was washed with EtOAc (4×10 mL)
  6. dry with materialThe combined organic solutions were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by medium pressure chromatography (EtOAc to 39:1 EtOAc:MeOH to 19:1 EtOAc:MeOH)

출처 및 근거

ORD 기록
ord-dd232c1fccbf4e4cb73c8f40d94a2c21
출처 데이터셋
uspto-grants-2004_05
특허 번호
US06737437B2

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