tert-butyl N-(furan-2-ylmethyl)carbamate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride (0.913 g, 1.68 mmol) (from Step E, Example 1) is dissolved in DMF (20 ml) and the solution is degassed under nitrogen. The above solution is added over 10 hours to a heated (110° C.) degassed suspension of tricyclohexyl phosphine (0.475 g, 1.7 mmol), palladium dichloride (15.2 mg, 0.086 mmol), potassium acetate (0.35 g, 3.6 mmol), tetra n-butyl ammonium bromide (0.552 g, 2.15 mmol), and Furan-2-ylmethyl-carbamic acid tert-butyl ester (2.9 g, 15 mmol) in DMF (5 ml). Heating is continued for 9 hours after the end of addition. The reaction mixture is cooled, diluted with water and extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution yields 0.450 g (0.78 mmol, 46%) of the clean desired product. the solution is degassed under nitrogen The above solution is added over 10 hours to degassed Heating after the end of addition The reaction mixture is cooled extracted with EtOAc The combined organic extracts are dried (Na2SO4) concentrated under reduced pressure Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride (0.913 g, 1.68 mmol) (from Step E, Example 1) is dissolved in DMF (20 ml) and the solution is degassed under nitrogen. The above solution is added over 10 hours to a heated (110° C.) degassed suspension of tricyclohexyl phosphine (0.475 g, 1.7 mmol), palladium dichloride (15.2 mg, 0.086 mmol), potassium acetate (0.35 g, 3.6 mmol), tetra n-butyl ammonium bromide (0.552 g, 2.15 mmol), and Furan-2-ylmethyl-carbamic acid tert-butyl ester (2.9 g, 15 mmol) in DMF (5 ml). Heating is continued for 9 hours after the end of addition. The reaction mixture is cooled, diluted with water and extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution yields 0.450 g (0.78 mmol, 46%) of the clean desired product. the solution is degassed under nitrogen The above solution is added over 10 hours to degassed Heating after the end of addition The reaction mixture is cooled extracted with EtOAc The combined organic extracts are dried (Na2SO4) concentrated under reduced pressure Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride (0.913 g, 1.68 mmol) (from Step E, Example 1) is dissolved in DMF (20 ml) and the solution is degassed under nitrogen. The above solution is added over 10 hours to a heated (110° C.) degassed suspension of tricyclohexyl phosphine (0.475 g, 1.7 mmol), palladium dichloride (15.2 mg, 0.086 mmol), potassium acetate (0.35 g, 3.6 mmol), tetra n-butyl ammonium bromide (0.552 g, 2.15 mmol), and Furan-2-ylmethyl-carbamic acid tert-butyl ester (2.9 g, 15 mmol) in DMF (5 ml). Heating is continued for 9 hours after the end of addition. The reaction mixture is cooled, diluted with water and extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution yields 0.450 g (0.78 mmol, 46%) of the clean desired product. the solution is degassed under nitrogen The above solution is added over 10 hours to degassed Heating after the end of addition The reaction mixture is cooled extracted with EtOAc The combined organic extracts are dried (Na2SO4) concentrated under reduced pressure Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-(tert-butoxycarbonylaminomethyl)-furan (9.8 g, 50 mmol) in 150 mL of dichloromethane was added into a flask, and the reaction mixture was cooled to 0° C. in an ice bath. A solution of pyridine-sulfur trioxide adduct (15.9 g, 100 mmol) in 100 mL of dichloromethane were added dropwise. Upon completion of the addition, the reaction mixture was allowed to warm to room temperature. The mixture was stirred at room temperature for additional 8 h. After the completion of the reaction, the reaction mixture was then extracted with water (400 mL×2). Aqueous hydrochloric acid (10%) was slowly added dropwise to the aqueous layer. The aqueous layer was adjusted to pH 6.5-7, and extracted with dichloromethane (500 mL×2). The organic layer was washed by saturated brine, and concentrated under reduced pressure to give 5.5 g (40.0% yield) of 5-(tert-butoxycarbonylaminomethyl)furan-2-sulfonic acid. Upon completion of the addition to warm to room temperature After the completion of the reaction the reaction mixture was then extracted with water (400 mL×2) Aqueous hydrochloric acid (10%) was slowly added dropwise to the aqueous layer extracted with dichloromethane (500 mL×2) The organic layer was washed by saturated brine concentrated under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride (0.913 g, 1.68 mmol) (from Step E, Example 1) is dissolved in DMF (20 ml) and the solution is degassed under nitrogen. The above solution is added over 10 hours to a heated (110° C.) degassed suspension of tricyclohexyl phosphine (0.475 g, 1.7 mmol), palladium dichloride (15.2 mg, 0.086 mmol), potassium acetate (0.35 g, 3.6 mmol), tetra n-butyl ammonium bromide (0.552 g, 2.15 mmol), and Furan-2-ylmethyl-carbamic acid tert-butyl ester (2.9 g, 15 mmol) in DMF (5 ml). Heating is continued for 9 hours after the end of addition. The reaction mixture is cooled, diluted with water and extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution yields 0.450 g (0.78 mmol, 46%) of the clean desired product. the solution is degassed under nitrogen The above solution is added over 10 hours to degassed Heating after the end of addition The reaction mixture is cooled extracted with EtOAc The combined organic extracts are dried (Na2SO4) concentrated under reduced pressure Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(6-iodo-quinazolin-4-yl)-amine hydrochloride (0.913 g, 1.68 mmol) (from Step E, Example 1) is dissolved in DMF (20 ml) and the solution is degassed under nitrogen. The above solution is added over 10 hours to a heated (110° C.) degassed suspension of tricyclohexyl phosphine (0.475 g, 1.7 mmol), palladium dichloride (15.2 mg, 0.086 mmol), potassium acetate (0.35 g, 3.6 mmol), tetra n-butyl ammonium bromide (0.552 g, 2.15 mmol), and Furan-2-ylmethyl-carbamic acid tert-butyl ester (2.9 g, 15 mmol) in DMF (5 ml). Heating is continued for 9 hours after the end of addition. The reaction mixture is cooled, diluted with water and extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated under reduced pressure. Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution yields 0.450 g (0.78 mmol, 46%) of the clean desired product. the solution is degassed under nitrogen The above solution is added over 10 hours to degassed Heating after the end of addition The reaction mixture is cooled extracted with EtOAc The combined organic extracts are dried (Na2SO4) concentrated under reduced pressure Flash chromatography on silica with 10-50% EtOAc:hexanes gradient elution