(R)-3-fluoro-4-(7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile → 3-fluoro-4-((5R,7S)-7-hydroxy-7-vinyl-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile

HRID 2036029

반응식

HRID 2036029 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C@@H:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[C:12](=[O:18])[CH2:11]1)[C:5]#[N:6].[CH:19]([Mg]Br)=[CH2:20]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[C@@H:10]1[N:14]2[CH:15]=[N:16][CH:17]=[C:13]2[C@@:12]([OH:18])([CH:19]=[CH2:20])[CH2:11]1)[C:5]#[N:6]

참가 물질

4

반응물 2

HCID 67216150(R)-3-fluoro-4-(7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrileHCID 178418507HCID 178418507, 화합물

생성물 1

HCID 532364363-fluoro-4-((5R,7S)-7-hydroxy-7-vinyl-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrile

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

To a stirred solution of 3-fluoro-4-((R)-7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-benzonitrile (0.6 g, 2.5 mmol), in THF (20 mL) cooled in a dry ice acetone bath under nitrogen was added via syringe a solution of vinyl magnesium bromide (0.7 M) in THF (4.3 mL, 3.0 mmol). The crude was warmed to room temperature in 3 hrs. The crude was quenched with NH4Cl aq. The crude was diluted in EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated. The crude was purified via preparation plate using 5% (2M NH3 in MeOH)/CH2Cl2 two times followed by purification using RPHPLC using 10% to 40% MeCN/H2O to give 142 mg of the entitled product as the major diastereomer. MS 270.2 (M+H); LCMS condition A, retention time 0.99 min. 1H NMR (400 MHz, CDCl3-d) ppm 2.56 (br. s., 1H), 2.68 (dd, 1H), 3.22 (dd, 1H), 5.24 (d, 1H), 5.41 (d, 1H), 5.59-5.73 (m, 1H), 6.10 (dd, 1H), 6.91 (br. s., 1H), 7.10 (t, 1H), 7.35 (d, 2H), 7.39 (br. s., 1H).

후처리

  1. customThe crude was quenched with NH4Cl aq. The crude
  2. additionwas diluted in EtOAc
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude was purified via preparation plate
  7. customfollowed by purification

출처 및 근거

ORD 기록
ord-8ec98856160b41dd82752e22df30581d
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575160B2

연결된 노트

불러오는 중…