methyl 3-aminofuran-2-carboxylate

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

Procedure: To a solution of methyl 3-aminofuran-2-carboxylate 34 (100 mg, 1.0 eq) in dichloromethane (3 ml) at −78° C. was added chlorosulfonyl isocyanate (0.09 ml, 1.4 eq) dropwise. The reaction was slowly warmed to room temperature and stirred for 40 minutes. Reaction was concentrated. To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes. Reaction mixture was allowed to cool down to room temperature, and was neutralized with saturated aq. NaHCO3. Solid was collected by filtration to yield ethyl 3-ureidofuran-2-carboxylate 35 (120 mg, 92%) as a beige solid which was used in the next reaction without further purification. Reaction was concentrated To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes Reaction mixture to cool down to room temperature Solid was collected by filtration

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

Procedure: Tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 1.0 eq) was dissolved in dichloromethane (8 ml) and treated with trifluoroacetic acid (5 ml). Reaction mixture was stirred at room temperature for 3 h, and was then concentrated. Residue was dissolved in dichloromethane and washed with saturated aq. NaHCO3. The organic layer was dried (Na2SO4) and concentrated Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield methyl 3-aminofuran-2-carboxylate 34 (574 mg, 86%): MS (Q1) 142 (M)+. Reaction mixture was then concentrated Residue was dissolved in dichloromethane washed with saturated aq. NaHCO3 The organic layer was dried (Na2SO4) concentrated Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: To a solution of methyl 3-aminofuran-2-carboxylate 34 (100 mg, 1.0 eq) in dichloromethane (3 ml) at −78° C. was added chlorosulfonyl isocyanate (0.09 ml, 1.4 eq) dropwise. The reaction was slowly warmed to room temperature and stirred for 40 minutes. Reaction was concentrated. To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes. Reaction mixture was allowed to cool down to room temperature, and was neutralized with saturated aq. NaHCO3. Solid was collected by filtration to yield ethyl 3-ureidofuran-2-carboxylate 35 (120 mg, 92%) as a beige solid which was used in the next reaction without further purification. Reaction was concentrated To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes Reaction mixture to cool down to room temperature Solid was collected by filtration

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

Procedure: Tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 1.0 eq) was dissolved in dichloromethane (8 ml) and treated with trifluoroacetic acid (5 ml). Reaction mixture was stirred at room temperature for 3 h, and was then concentrated. Residue was dissolved in dichloromethane and washed with saturated aq. NaHCO3. The organic layer was dried (Na2SO4) and concentrated Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield methyl 3-aminofuran-2-carboxylate 34 (574 mg, 86%): MS (Q1) 142 (M)+. Reaction mixture was then concentrated Residue was dissolved in dichloromethane washed with saturated aq. NaHCO3 The organic layer was dried (Na2SO4) concentrated Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: Tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 1.0 eq) was dissolved in dichloromethane (8 ml) and treated with trifluoroacetic acid (5 ml). Reaction mixture was stirred at room temperature for 3 h, and was then concentrated. Residue was dissolved in dichloromethane and washed with saturated aq. NaHCO3. The organic layer was dried (Na2SO4) and concentrated Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield methyl 3-aminofuran-2-carboxylate 34 (574 mg, 86%): MS (Q1) 142 (M)+. Reaction mixture was then concentrated Residue was dissolved in dichloromethane washed with saturated aq. NaHCO3 The organic layer was dried (Na2SO4) concentrated Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: A suspension of 6-chloro-7-deazapurine (100.00 mg; 0.65 mmol), methyl 3-amino-2-furoate (138 mg; 0.98 mmol) and concentrated hydrochloric acid (55 μL; 0.65 mmol) in tert-butanol (2 mL) was microwaved at 75° C. for 3 h. The reaction mixture was diluted with methanol (2 mL) and purified by chromatography on a SP1 Biotage system, using dichloromethane and methanol as eluents to afford 3-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-furan-2-carboxylic acid methyl ester (30 mg, 18%) as a white solid. (HPLC: 99%, RT: 5.43 min). 1H NMR (DMSO-d6) 12.03 (br s, 1H), 8.99 (br s, 1H), 8.40 (s, 1H), 7.90 (d, J=2.2 Hz, 1H), 7.71 (d, J=1.8 Hz, 1H), 7.38 (dd, J=3.3, 2.2 Hz, 1H), 6.60 (dd, J=3.3, 1.8 Hz, 1H), 3.90 (s, 3H); MS (m/z) 259 [M+H]+. was microwaved at 75° C. for 3 h purified by chromatography on a SP1 Biotage system

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

Procedure: To a solution of methyl 3-aminofuran-2-carboxylate 34 (100 mg, 1.0 eq) in dichloromethane (3 ml) at −78° C. was added chlorosulfonyl isocyanate (0.09 ml, 1.4 eq) dropwise. The reaction was slowly warmed to room temperature and stirred for 40 minutes. Reaction was concentrated. To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes. Reaction mixture was allowed to cool down to room temperature, and was neutralized with saturated aq. NaHCO3. Solid was collected by filtration to yield ethyl 3-ureidofuran-2-carboxylate 35 (120 mg, 92%) as a beige solid which was used in the next reaction without further purification. Reaction was concentrated To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes Reaction mixture to cool down to room temperature Solid was collected by filtration

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

Procedure: To a solution of methyl 3-aminofuran-2-carboxylate 34 (100 mg, 1.0 eq) in dichloromethane (3 ml) at −78° C. was added chlorosulfonyl isocyanate (0.09 ml, 1.4 eq) dropwise. The reaction was slowly warmed to room temperature and stirred for 40 minutes. Reaction was concentrated. To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes. Reaction mixture was allowed to cool down to room temperature, and was neutralized with saturated aq. NaHCO3. Solid was collected by filtration to yield ethyl 3-ureidofuran-2-carboxylate 35 (120 mg, 92%) as a beige solid which was used in the next reaction without further purification. Reaction was concentrated To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes Reaction mixture to cool down to room temperature Solid was collected by filtration

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

Procedure: Tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate 33 (1.14 g, 1.0 eq) was dissolved in dichloromethane (8 ml) and treated with trifluoroacetic acid (5 ml). Reaction mixture was stirred at room temperature for 3 h, and was then concentrated. Residue was dissolved in dichloromethane and washed with saturated aq. NaHCO3. The organic layer was dried (Na2SO4) and concentrated Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield methyl 3-aminofuran-2-carboxylate 34 (574 mg, 86%): MS (Q1) 142 (M)+. Reaction mixture was then concentrated Residue was dissolved in dichloromethane washed with saturated aq. NaHCO3 The organic layer was dried (Na2SO4) concentrated Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: To a solution of methyl 3-aminofuran-2-carboxylate (100 mg, 1.0 eq) in dichloromethane (3 ml) at −78° C. was added chlorosulfonyl isocyanate (0.09 ml, 1.4 eq) dropwise. The reaction was slowly warmed to room temperature and stirred for 40 minutes. Reaction was concentrated. To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes. Reaction mixture was allowed to cool down to room temperature, and was neutralized with saturated aq. NaHCO3. Solid was collected by filtration to yield ethyl 3-ureidofuran-2-carboxylate (120 mg, 92%) as a beige solid which was used in the next reaction without further purification. Reaction was concentrated To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes Reaction mixture to cool down to room temperature Solid was collected by filtration

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

Procedure: Tert-butyl 2-(methoxycarbonyl)furan-3-ylcarbamate (1.14 g, 1.0 eq) was dissolved in dichloromethane (8 ml) and treated with trifluoroacetic acid (5 ml). Reaction mixture was stirred at room temperature for 3 h, and was then concentrated. Residue was dissolved in dichloromethane and washed with saturated aq. NaHCO3. The organic layer was dried (Na2SO4) and concentrated Mixture was extracted with ethyl acetate. The combined organic extracts were dried with Na2SO4 and concentrated. The crude reaction mixture was purified by flash chromatography to yield methyl 3-aminofuran-2-carboxylate (574 mg, 86%): MS (Q1) 142 (M)+. Reaction mixture was then concentrated Residue was dissolved in dichloromethane washed with saturated aq. NaHCO3 The organic layer was dried (Na2SO4) concentrated Mixture was extracted with ethyl acetate The combined organic extracts were dried with Na2SO4 concentrated The crude reaction mixture was purified by flash chromatography

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

Procedure: To a solution of methyl 3-aminofuran-2-carboxylate 34 (100 mg, 1.0 eq) in dichloromethane (3 ml) at −78° C. was added chlorosulfonyl isocyanate (0.09 ml, 1.4 eq) dropwise. The reaction was slowly warmed to room temperature and stirred for 40 minutes. Reaction was concentrated. To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes. Reaction mixture was allowed to cool down to room temperature, and was neutralized with saturated aq. NaHCO3. Solid was collected by filtration to yield ethyl 3-ureidofuran-2-carboxylate 35 (120 mg, 92%) as a beige solid which was used in the next reaction without further purification. Reaction was concentrated To the residue was added 6N HCl (3.5 ml) and mixture was heated to 100° C. for 20 minutes Reaction mixture to cool down to room temperature Solid was collected by filtration