3-ethyl-1,3-thiazolidine-2,4-dione

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 50 ml three necked round bottom flask, 4-(7-pivaloyl-5-((2-(trimethylsilyl)-ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-2-ylamino)benzaldehyde (0.104 g, 0.00023 mole) and 3-ethylthiazolidine-2,4-dione (0.067 g, 0.00046 mole) was taken in ethanol (3 ml). Piperidine acetate (3.3 M solution in water) (0.1 ml) was added dropwise at RT. The reaction mixture was refluxed for 6 hrs. After completion of the reaction, ethanol was distilled out and water was added to residue. Aq. layer was extracted with ethyl acetate, the combined organic layers were dried over Na2SO4, filtered and concentrated to afford crude product which was purified by triturated with n-pentane. The solid was filtered and dried under vacuum to yield 0.070 g of 3-ethyl-5-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzylidene)thiazolidine-2,4-dione which was converted to the title compounds as described in Example 6 above. The reaction mixture was refluxed for 6 hrs was distilled out and water was added to residue Aq. layer was extracted with ethyl acetate the combined organic layers were dried over Na2SO4 filtered concentrated to afford crude product which was purified by triturated with n-pentane The solid was filtered dried under vacuum

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 100 ml three necked round bottom flask, sodium hydride (60% in paraffin) (0.188 g, 0.00470 mole) was taken in DMF (2.0 ml). Thiazolidine-2,4-dione (0.5 g, 0.00427 mole) in DMF (3 ml) was slowly added at 0° C. over 15 min under nitrogen atmosphere. After addition was complete, the reaction mixture was stirred for 1 hr at 50° C. The reaction was then cooled to 0° C., followed by drop wise addition of ethyl iodide (0.41 ml, 0.00512 mole) at 0° C. The reaction mixture was warmed up to RT and stirred for 1 hr. After completion of the reaction, the reaction mixture was poured in water and aq. layer was extracted with ethyl acetate. Organic layers were combined and washed with brine solution, dried over Na2SO4, filtered and concentrated to afford crude product which was purified using column purification by eluting the compound with 5% ethyl acetate in hexanes to yield 0.5 g of 3-ethylthiazolidine-2,4-dione. After addition The reaction was then cooled to 0° C. The reaction mixture was warmed up to RT stirred for 1 hr After completion of the reaction aq. layer was extracted with ethyl acetate washed with brine solution dried over Na2SO4 filtered concentrated to afford crude product which was purified column purification by eluting the compound with 5% ethyl acetate in hexanes

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 100 ml three necked round bottom flask, sodium hydride (60% in paraffin) (0.188 g, 0.00470 mole) was taken in DMF (2.0 ml). Thiazolidine-2,4-dione (0.5 g, 0.00427 mole) in DMF (3 ml) was slowly added at 0° C. over 15 min under nitrogen atmosphere. After addition was complete, the reaction mixture was stirred for 1 hr at 50° C. The reaction was then cooled to 0° C., followed by drop wise addition of ethyl iodide (0.41 ml, 0.00512 mole) at 0° C. The reaction mixture was warmed up to RT and stirred for 1 hr. After completion of the reaction, the reaction mixture was poured in water and aq. layer was extracted with ethyl acetate. Organic layers were combined and washed with brine solution, dried over Na2SO4, filtered and concentrated to afford crude product which was purified using column purification by eluting the compound with 5% ethyl acetate in hexanes to yield 0.5 g of 3-ethylthiazolidine-2,4-dione. After addition The reaction was then cooled to 0° C. The reaction mixture was warmed up to RT stirred for 1 hr After completion of the reaction aq. layer was extracted with ethyl acetate washed with brine solution dried over Na2SO4 filtered concentrated to afford crude product which was purified column purification by eluting the compound with 5% ethyl acetate in hexanes

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 50 ml three necked round bottom flask, 4-(7-pivaloyl-5-((2-(trimethylsilyl)-ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-2-ylamino)benzaldehyde (0.104 g, 0.00023 mole) and 3-ethylthiazolidine-2,4-dione (0.067 g, 0.00046 mole) was taken in ethanol (3 ml). Piperidine acetate (3.3 M solution in water) (0.1 ml) was added dropwise at RT. The reaction mixture was refluxed for 6 hrs. After completion of the reaction, ethanol was distilled out and water was added to residue. Aq. layer was extracted with ethyl acetate, the combined organic layers were dried over Na2SO4, filtered and concentrated to afford crude product which was purified by triturated with n-pentane. The solid was filtered and dried under vacuum to yield 0.070 g of 3-ethyl-5-(4-(7-pivaloyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-ylamino)benzylidene)thiazolidine-2,4-dione which was converted to the title compounds as described in Example 6 above. The reaction mixture was refluxed for 6 hrs was distilled out and water was added to residue Aq. layer was extracted with ethyl acetate the combined organic layers were dried over Na2SO4 filtered concentrated to afford crude product which was purified by triturated with n-pentane The solid was filtered dried under vacuum

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 100 ml three necked round bottom flask, sodium hydride (60% in paraffin) (0.188 g, 0.00470 mole) was taken in DMF (2.0 ml). Thiazolidine-2,4-dione (0.5 g, 0.00427 mole) in DMF (3 ml) was slowly added at 0° C. over 15 min under nitrogen atmosphere. After addition was complete, the reaction mixture was stirred for 1 hr at 50° C. The reaction was then cooled to 0° C., followed by drop wise addition of ethyl iodide (0.41 ml, 0.00512 mole) at 0° C. The reaction mixture was warmed up to RT and stirred for 1 hr. After completion of the reaction, the reaction mixture was poured in water and aq. layer was extracted with ethyl acetate. Organic layers were combined and washed with brine solution, dried over Na2SO4, filtered and concentrated to afford crude product which was purified using column purification by eluting the compound with 5% ethyl acetate in hexanes to yield 0.5 g of 3-ethylthiazolidine-2,4-dione. After addition The reaction was then cooled to 0° C. The reaction mixture was warmed up to RT stirred for 1 hr After completion of the reaction aq. layer was extracted with ethyl acetate washed with brine solution dried over Na2SO4 filtered concentrated to afford crude product which was purified column purification by eluting the compound with 5% ethyl acetate in hexanes