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 923282노트

반응식

HRID 923282 반응식
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

참가 물질

4

반응물 2

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-9e7b0e609811469da5b3f516e5dc0313
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09278969B2

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