6-[5-(3-Chloropropyl)imidazol-1-ylmethyl]biphenyl-3-carbonitrile → 6-(5,6,7,8-Tetrahydroimidazo[1,5-a]pyridin-5-yl)biphenyl-3-carbonitrile

HRID 923282Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 923282
Cl[CH2:2][CH2:3][CH2:4][C:5]1[N:9]([CH2:10][C:11]2[C:16]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[CH:15][C:14]([C:23]#[N:24])=[CH:13][CH:12]=2)[CH:8]=[N:7][CH:6]=1.CC([O-])(C)C.[K+].C1COCC1>C1COCC1>[CH:6]1[N:7]=[CH:8][N:9]2[CH:10]([C:11]3[C:16]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:15][C:14]([C:23]#[N:24])=[CH:13][CH:12]=3)[CH2:2][CH2:3][CH2:4][C:5]=12

Komponenten

4

Edukt 2

HCID 588270706-[5-(3-Chloropropyl)imidazol-1-ylmethyl]biphenyl-3-carbonitrileHCID 66863523KOtBu THF

Produkt 1

HCID 588270486-(5,6,7,8-Tetrahydroimidazo[1,5-a]pyridin-5-yl)biphenyl-3-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 6-[5-(3-chloropropyl)imidazol-1-ylmethyl]biphenyl-3-carbonitrile (1.0 g, 3.0 mmol) in THF (16 mL) at 0° C. is added t-BuOK/THF (1.0 M, 6 mL, 6.0 mmol). The mixture is warmed up to ambient temperature and stirred for 2 h. The reaction mixture is quenched by saturated aqueous NH4Cl and partitioned between CH2Cl2 and brine. The organic layer is washed by brine, dried over anhydrous Na2SO4 and concentrated to give the crude oil, which is subjected to flash chromatography (silica gel) eluting with MeOH:CH2Cl2 to yield the desired compound. MS (ESI) m/z 300 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 1.50-1.66 (m, 1H), 1.73-1.83 (m, 1H), 1.83-1.95 (m, 1H), 1.95-2.16 (m, 1H), 2.68-2.95 (m, 2H), 5.28 (dd, J=8.5, 5.2 Hz, 1H), 6.83 (s, 1H), 7.01-7.15 (m, 2H), 7.27-7.35 (m, 2H), 7.43-7.54 (m, 3H), 7.58 (s, 1H), 7.62 (d, J=8.3 Hz, 1H). Resolution of the enantiomers of the title compound is achieved by Chiral HPLC using the ChiralPak AD column with a 20% IPA/Hexane mobile phase.

Aufarbeitung

  1. customThe reaction mixture is quenched by saturated aqueous NH4Cl
  2. custompartitioned between CH2Cl2 and brine
  3. washThe organic layer is washed by brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customto give the crude oil, which
  7. washeluting with MeOH

Quellen und Nachweise

ORD-Eintrag
ord-9e7b0e609811469da5b3f516e5dc0313
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09278969B2

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