1-(1,1-Difluoroethyl)-4-iodobenzene → 4-((5R,7S)-7-(4-(1,1-difluoroethyl)phenyl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile

HRID 2036031

反応式

HRID 2036031 の反応式
[F:1][C:2]([C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1)([F:4])[CH3:3].C([Mg]Cl)(C)C.[F:17][C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[C@@H:26]1[N:30]2[CH:31]=[N:32][CH:33]=[C:29]2[C:28](=[O:34])[CH2:27]1)[C:21]#[N:22]>C1COCC1>[F:1][C:2]([C:5]1[CH:10]=[CH:9][C:8]([C@:28]2([OH:34])[C:29]3[N:30]([CH:31]=[N:32][CH:33]=3)[C@@H:26]([C:25]3[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][C:18]=3[F:17])[CH2:27]2)=[CH:7][CH:6]=1)([F:4])[CH3:3]

参加物

5

反応物 3

HCID 667620211-(1,1-Difluoroethyl)-4-iodobenzeneHCID 67216150(R)-3-fluoro-4-(7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)benzonitrileHCID 178418918HCID 178418918、化合物

生成物 1

HCID 532364384-((5R,7S)-7-(4-(1,1-difluoroethyl)phenyl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile収率 18.6%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
-40 °C

実験手順

To a solution of 1-(1,1-difluoro-ethyl)-4-iodo-benzene, (167 mg, 0.62 mmol) in THF (2 mL) cooled to −40° C. was added a 2 M solution of i-PrMgCl in THF (0.42 mL, 0.83 mmol) dropwise. The crude was stirred at −40° C. for 1 hr. 3-fluoro-4-((R)-7-oxo-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-benzonitrile (125 mg, 0.52 mmol) in THF (2 mL) was added. The crude was allowed to slowly warm to room temperature over 3 hrs. The crude was quenched with NH4Cl aq. The crude diluted in EtOAc. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated. The crude was purified via preparation plate two times using 2M NH3 in MeOH/CH2Cl2 to give 37 mgs of the entitled product. MS 384.3 (M+H); LCMS condition A, retention time 1.31 min. 1H NMR (400 MHz, CDCl3) δ ppm 1.83 (t, 3H), 2.94 (dd, 1H), 3.24 (dd, 1H), 5.70 (d, 1H), 6.47 (s, 1H), 7.11 (t, 1H), 7.19 (s, 1H), 7.33 (d, 2H), 7.38 (m, 2H), 7.46 (m, 2H).

後処理

  1. temperatureto slowly warm to room temperature over 3 hrs
  2. customThe crude was quenched with NH4Cl aq. The crude
  3. additiondiluted in EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified via preparation plate two times

出典と根拠

ORDレコード
ord-fd7b4866f0df4a9296ca825142e5d7f6
出典データセット
uspto-grants-2013_11
特許番号
US08575160B2

関連ノート

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