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

HRID 1177514Notes

Reaction equation

HRID 1177514 reaction equation
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

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-fe052c25c4ee4f9d8a5d2c8e64a0bc85
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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