Sodium hydride → 1,1-Dimethylethyl 3-(5-{5-[3-cyano-4-(3-fluoro-1-pyrrolidinyl)phenyl]-1,2,4-oxadiazol-3-yl}-1-isoquinolinyl)propanoate

HRID 2192507Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2192507
[F:1][CH:2]1[CH2:6][CH2:5][NH:4][CH2:3]1.[H-].[Na+].[C:9]([C:11]1[CH:12]=[C:13]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:24]=3[CH:25]=[CH:26][N:27]=[C:28]4[CH2:33][CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[N:19]=2)[CH:14]=[CH:15][C:16]=1F)#[N:10]>CN(C=O)C>[C:9]([C:11]1[CH:12]=[C:13]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:24]=3[CH:25]=[CH:26][N:27]=[C:28]4[CH2:33][CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[N:19]=2)[CH:14]=[CH:15][C:16]=1[N:4]1[CH2:5][CH2:6][CH:2]([F:1])[CH2:3]1)#[N:10]

Komponenten

5

Edukt 3

HCID 24758Sodium hydride2×HCID 3744989Pyrrolidine, 3-fluoro-HCID 581499101,1-Dimethylethyl 3-{5-[5-(3-cyano-4-fluorophenyl)-1,2,4-oxadiazol-3-yl]-1-isoquinolinyl}propanoate

Produkt 1

HCID 581499051,1-Dimethylethyl 3-(5-{5-[3-cyano-4-(3-fluoro-1-pyrrolidinyl)phenyl]-1,2,4-oxadiazol-3-yl}-1-isoquinolinyl)propanoateAusbeute 21 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 3-fluoropyrrolidine (Anichem Product List; 16.39 mg, 0.130 mmol) in DMF (2.5 ml) was cooled in an ice bath and sodium hydride (6.89 mg, 0.172 mmol) was added. The mixture was stirred for 10 mins then 1,1-dimethylethyl 3-{5-[5-(3-cyano-4-fluorophenyl)-1,2,4-oxadiazol-3-yl]-1-isoquinolinyl}propanoate (D50; 58 mg, 0.130 mmol) was added. The ice bath was removed and the solution was stirred at room temperature for 3 hrs. Further sodium hydride (3.13 mg, 0.078 mmol) was added and the resulting solution was stirred at room temperature overnight. The mixture was partitioned between ethyl acetate and brine. The organic layer was dried with magnesium sulphate and concentrated under vacuum. The residue was purified by Mass-Directed Auto-Preparative HPLC (formic acid modifier) to provide the title compound as a cream solid (14 mg).

Aufarbeitung

  1. customThe ice bath was removed
  2. stirringthe solution was stirred at room temperature for 3 hrs
  3. stirringthe resulting solution was stirred at room temperature overnight
  4. customThe mixture was partitioned between ethyl acetate and brine
  5. dry with materialThe organic layer was dried with magnesium sulphate
  6. concentrationconcentrated under vacuum
  7. customThe residue was purified by Mass-Directed Auto-Preparative HPLC (formic acid modifier)

Quellen und Nachweise

ORD-Eintrag
ord-9df46e3e6782486baa6da6e702e2e47f
Quelldatensatz
uspto-grants-2012_12
Patentnummer
US08329730B2

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