Trifluoroacetic anhydride → 2-(7-Chloro-thieno[3,2-b]pyridin-2-yl)-thiazole-4-carboxylic acid ethyl ester

HRID 889892Notes

Reaction equation

HRID 889892 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11](=[S:13])[NH2:12])[S:10][C:3]=12.Br[CH2:15][C:16](=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18].FC(F)(F)C(OC(=O)C(F)(F)F)=O.[NH4+].[OH-]>C1COCC1.CO.C(Cl)(Cl)Cl>[NH4+:5].[OH-:18].[CH2:20]([O:19][C:17]([C:16]1[N:12]=[C:11]([C:9]2[S:10][C:3]3[C:4](=[N:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH:8]=2)[S:13][CH:15]=1)=[O:18])[CH3:21]

Participants

9

Reactant 4

HCID 9845Trifluoroacetic anhydrideHCID 14923Ammonium HydroxideHCID 66144Ethyl bromopyruvateHCID 235951097-Chlorothieno[3,2-b]pyridine-2-carbothioamide

Product 2

HCID 14923Ammonium HydroxideHCID 695858522-(7-Chloro-thieno[3,2-b]pyridin-2-yl)-thiazole-4-carboxylic acid ethyl esterYield 96.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-Chloro-thieno[3,2-b]pyridine-2-carbothioic acid amide (5.00 g, 21.9 mmol) in 60 mL of THF was added ethyl bromopyruvate (4.11 mL, 32.8 mmol). The reaction mixture was stirred at room temperature under nitrogen overnight. The reaction mixture was cooled to 0° C., and 30 mL trifluoroacetic anhydride was added. The reaction was stirred at room temperature for four hours then cooled to 0° C. The reaction was treated with 30 mL of concentrated NH4OH followed by removal of THF under reduced pressure. The dark, oily residue was partitioned between water and ethyl acetate. The aqueous layer was separated and washed with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and evaporated under reduced pressure to give a brown oily residue. Chromotography (99.5:0.45:0.05 CHCl3:CH3OH:NH4OH) over silica gel gave a 67% of 2-(7-Chloro-thieno[3,2-b]pyridin-2-yl)-thiazole-4-carboxylic acid ethyl ester (3.42 g) as a pale yellow solid. C13H9ClN2O2S2: APCI m/z 325.0/327.0 (MH+); 232.9/325.9 (neg.); 1H NMR (d6-DMSO): δ 8.67 (d, 1H, J=5.0 Hz), 8.37 (s, 1H), 7.62 (d, 1H, J=5.0 Hz), 3.98 (q, 2H, J=7.0 Hz), 1.13 (t, 3H, J=7.0 Hz) ppm.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringThe reaction was stirred at room temperature for four hours
  3. temperaturethen cooled to 0° C
  4. customfollowed by removal of THF under reduced pressure
  5. customThe dark, oily residue was partitioned between water and ethyl acetate
  6. customThe aqueous layer was separated
  7. washwashed with ethyl acetate
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over magnesium sulfate
  10. customevaporated under reduced pressure
  11. customto give a brown oily residue

Sources & evidence

ORD record
ord-cea17a0c8f9046ff9361459deb49db6a
Source dataset
uspto-grants-2006_02
Patent number
US06995171B2

Reaction notes

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