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

HRID 1177390Notes

Reaction equation

HRID 1177390 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[C:21]1[C:26]([N:27]=[C:28]=[S:29])=[CH:25][CH:24]=[C:23]([Cl:30])[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:28]2[S:29][C:21]3[C:26]([N:27]=2)=[CH:25][CH:24]=[C:23]([Cl:30])[N:22]=3)=[C:3]([F:14])[CH:4]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 671119942-(4-Bromo-3-fluorophenyl)-1,3-dioxaneHCID 71519260HCID 71519260, compoundHCID 178418339Butyllithium

Product 1

HCID 591748622-(4-(1,3-Dioxan-2-yl)-2-fluorophenyl)-5-chlorothiazolo[5,4-b]pyridine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2-(4-bromo-3-fluorophenyl)-1,3-dioxane (7.65 g, 29.3 mmol) in 75 mL THF under argon at −78° C. was added 1-butyllithium 2.5M in hexanes (12.9 mL, 32.2 mmol) in portions over ˜20 min. The reaction mixture was allowed to stir 20 min, and was yellow. A solution of 2,6-dichloro-3-isothiocyanatopyridine (6.01 g, 29.3 mmol) in 20 mL THF was added dropwise via cannula. The resulting dark brown solution was allowed to stir 15 min, then was quenched by addition of sat'd aq. NH4Cl. The reaction mixture was partitioned between sat'd aq. NH4Cl and Et2O. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to give an orange solid. The solid was treated with sodium carbonate (4.66 g, 44.0 mmol) and approximately 15 mL DMF, and stirred under nitrogen at 90° C. The reaction was heated overnight, and in the morning was a solid mass. The reaction was diluted with water, stirred rapidly for several hours, and filtered, rinsing with water and MeOH. The resulting solid was dried in vacuo to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-5-chlorothiazolo[5,4-b]pyridine. MS (ESI) m/z: Calculated: 350.0; Observed: 350.9 (M++1).

Workup

  1. stirringto stir 15 min
  2. customwas quenched by addition of sat'd aq. NH4Cl
  3. customThe reaction mixture was partitioned between sat'd aq. NH4Cl and Et2O
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give an orange solid
  9. stirringstirred under nitrogen at 90° C
  10. temperatureThe reaction was heated overnight
  11. stirringstirred rapidly for several hours
  12. filtrationfiltered
  13. washrinsing with water and MeOH
  14. customThe resulting solid was dried in vacuo

Sources & evidence

ORD record
ord-68ebd1deac974570b9af03ae594c0726
Source dataset
uspto-grants-2010_11
Patent number
US07842685B2

Reaction notes

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