Sodium Carbonate → 2-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-6-chlorothiazolo[4,5-c]pyridine

HRID 1177514ノート

反応式

HRID 1177514 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[O:13][CH2:12][CH2:11][CH2:10][O:9]2)=[CH:4][C:3]=1[F:14].C([Li])CCC.[Cl:20][C:21]1[CH:26]=[C:25](Cl)[C:24]([N:28]=[C:29]=[S:30])=[CH:23][N:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.CN(C=O)C>[O:9]1[CH2:10][CH2:11][CH2:12][O:13][CH:8]1[C:5]1[CH:6]=[CH:7][C:2]([C:29]2[S:30][C:25]3[CH:26]=[C:21]([Cl:20])[N:22]=[CH:23][C:24]=3[N:28]=2)=[C:3]([F:14])[CH:4]=1

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 671119942-(4-Bromo-3-fluorophenyl)-1,3-dioxaneHCID 866387192,4-Dichloro-5-isothiocyanatopyridineHCID 178418339Butyllithium

生成物 1

HCID 866387202-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-6-chlorothiazolo[4,5-c]pyridine

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
80 °C

実験手順

To a solution of 2-(4-bromo-3-fluorophenyl)-1,3-dioxane (3.12 g, 11.9 mmol) in 40 mL THF at −78° C. under argon was added butyllithium, 2.5 M solution in hexanes (5.26 mL, 13.1 mmol) slowly dropwise. The resulting solution was allowed to stir 1 h at −78° C., at which point a solution at ambient temp of 2,4-dichloro-5-isothiocyanatopyridine (2.45 g, 11.9 mmol) in 10 mL THF was added slowly via cannula. The dark red reaction mixture was allowed to stir 15 min, and was then removed from the bath and quenched by slow addition of sat'd aq. NH4Cl. The reaction mixture was diluted with 40 mL MTBE, and the organic layer washed with water, brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The resulting material was treated with sodium carbonate (1.90 g, 17.9 mmol) and 10 mL DMF. The reaction was heated under nitrogen to 80° C. An additional 5 mL DMF was added to give a stirrable slurry. After 30 min additional, the reaction mixture was cooled slightly and treated with 100 mL water. After 10 min stirring, the mixture was filtered, rinsing with water and MeOH. The solid was collected and dried in vacuo overnight to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-6-chlorothiazolo[4,5-c]pyridine as a tan solid. MS (ESI) m/z: calculated: 350.0; Observed: 351.0 (M++1).

後処理

  1. additionwas added slowly via cannula
  2. customThe dark red reaction mixture
  3. customwas then removed from the bath
  4. customquenched by slow addition of sat'd aq. NH4Cl
  5. additionThe reaction mixture was diluted with 40 mL MTBE
  6. washthe organic layer washed with water, brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a stirrable slurry
  11. waitAfter 30 min additional
  12. temperaturethe reaction mixture was cooled slightly
  13. stirringAfter 10 min stirring
  14. filtrationthe mixture was filtered
  15. washrinsing with water and MeOH
  16. customThe solid was collected
  17. customdried in vacuo overnight

出典と根拠

ORDレコード
ord-fe052c25c4ee4f9d8a5d2c8e64a0bc85
出典データセット
uspto-grants-2010_11
特許番号
US07842685B2

反応ノート

読み込み中…