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 76899ノート

反応式

HRID 76899 の反応式
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

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-779b67b4736b45a9b22789fb2be71c67
出典データセット
uspto-grants-2014_09
特許番号
US08835646B2

反応ノート

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