benzyl N-prop-2-enylcarbamate

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

Procedure: To a solution of allylamine (58 mmoles, 3.34 g) at 0° C. in dichloromethane (100 mL) was added triethylamine (120 mmoles, 16 mL). The mixture was stirred for two minutes, then benzylchloroformate (58 mmoles, 8.25 mL) added dropwise. The resulting solution was stirred at 0° C. for 2 hours, and at ambient temperature for an additional 90 minutes. A white precipitate formed, which was filtered off. Solvent was removed from the filtrate under reduced pressure, and the residue chromatographed on a silica gel column, eluting with 20% ethyl acetate/hexanes, to give benzyl allylcarbamate, a compound of formula (2), as a clear oil. Yield: 5.0 g. The resulting solution was stirred at 0° C. for 2 hours at ambient temperature for an additional 90 minutes A white precipitate formed which was filtered off Solvent was removed from the filtrate under reduced pressure the residue chromatographed on a silica gel column eluting with 20% ethyl acetate/hexanes

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

Procedure: Scheme Vc, step A: 2-(4-Iodophenyl) propyl isopropylsulfonamide (1.5 g, 4.1 mmol), (phenylmethoxy)-N-prop-2-enylcarboxamide (0.94 g, 4.9 mmol, prepared in example 8), 9-BBN dimer (0.8 g, 3.28 mmol), [1,1′bis(diphenylphosphino)-ferrocene] dichloropalladium (II), PdCl2(dppf) (0.17 g, 0.2 mmol), 3N sodium hydroxide (3 mL), and pH=7 buffer: hydrogen peroxide (2:1, 15 mL) were combined in a manner analogous to the procedure described in example 6 to provide the intermediate title compound, N-{3-[4-(1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]propyl}(phenylmethoxy)carboxamide, (1.74 g, 99%). Electron spray M.S. 431 (M*−H).

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

Procedure: N-[3-(4-Bromophenyl)propyl](phenylmethoxy)carboxamide (1.5 g, 4.3 mmol), (phenylmethoxy)-N-eth-2-enylcarboxamide (0.92 g, 5.17 mmol, prepared in example 8), 9-BBN-dimer (0.84 g, 3.45 mmol), [1,1′bis(diphenylphosphino)-ferrocene] dichloropalladium (11), PdCl2(dppf), (0.175 9, 0.22 mmol), 3N sodium hydroxide (3 mL), and pH=7 buffer hydrogen peroxide (2:1, 10 mL) were combined in a manner analogous to the procedure described in example 6 to provide the intermediate title compound, (phenylmethoxy)-N-[3-(4-{2-[(phenylmethoxy)carbonylamino]ethyl}phenyl)propyl]carboxamide, (0.68 g, 35%). Electron spray M.S. 447 (M*+H).

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

Procedure: Scheme IVc, step A: 1,4-Dibromobenzene (2 g, 8.5 mmol), (phenylmethoxy)-N-prop-2-enylcarboxamide (1.95 g, 10.1 mmol, prepared in example 8), 9-BBN-dimer (2.7 g, 11 mmol), [1,1′bis(diphenylphosphino)-ferrocene] dichloropalladium (II), PdCl2(dppf), (0.35 g, 0.42 mmol), 3N sodium hydroxide (3 mL), and pH=7 buffer hydrogen peroxide (2:1, 10 mL) were combined in a manner analogous to the procedure described in example 6 to provide the intermediate title compound, N-[3-(4-bromophenyl)propyl](phenylmethoxy)carboxamide, (1.6 g, 54%). Electron spray M.S. 348 (M*+2).

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

Procedure: Scheme IIIb, step A: 4-Bromo-2-fluorobenzonitrile (3 g, 15 mmol), (phenylmethoxy)-N-prop-2-enylcarboxamide (3.44 g, 18 mmol), 9-BBN dimer (2.93 g, 12 mmol), [1,1′bis(diphenylphosphino)ferrocene] dichloropalladium (II), PdCl2(dppf) (0.61 g, 0.75 mmol), 3N sodium hydroxide (10 mL), and pH=7 buffer: hydrogen peroxide (2:1, 20 mL) are combined in a manner analogous to the procedure described in example 6 to provide the intermediate title compound, N-[3-(4-cyano-3-fluorophenyl)propyl](phenylmethoxy)carboxamide, (4.18, 89%). Electron spray M.S. 313 (M*+H).

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 250 mL single neck flask were placed allylamine (5 mL, 66.6 mmol) and triethylamine (11.1 mL, 80 mmol) in methylene chloride (80 mL). The mixture was cooled to −5° C. before being treated with benzylchloroformate (10 mL, 70 mmol) gradually. The reaction mixture was warmed up to RT while stirring overnight. The product was extracted with EtOAc and the organic layer was separated and washed twice with H2O, dried over anhydrous Na2SO4, filtered, and concentrated under reduced vacuum. The resulting oil was further purified via flash chromatography (Silica gel, isocratic) and eluting with a solvent of Hexanes/EtOAc 20% to provide the intermediate title compound, (phenylmethoxy)-N-prop-2-enylcarboxamide, (8.7 g, 68%) as oil. Electron spray M.S. 192 (M*+1). Into a 250 mL single neck flask were placed The reaction mixture was warmed up to RT The product was extracted with EtOAc the organic layer was separated washed twice with H2O dried over anhydrous Na2SO4 filtered concentrated under reduced vacuum The resulting oil was further purified via flash chromatography (Silica gel, isocratic) eluting with a solvent of Hexanes/EtOAc 20%

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

Procedure: To a solution of allylamine (58 mmoles, 3.34 g) at 0° C. in dichloromethane (100 mL) was added triethylamine (120 mmoles, 16 mL). The mixture was stirred for two minutes, then benzylchloroformate (58 mmoles, 8.25 mL) added dropwise. The resulting solution was stirred at 0° C. for 2 hours, and at ambient temperature for an additional 90 minutes. A white precipitate formed, which was filtered off. Solvent was removed from the filtrate under reduced pressure, and the residue chromatographed on a silica gel column, eluting with 20% ethyl acetate/hexanes, to give benzyl allylcarbamate, a compound of formula (2), as a clear oil. Yield: 5.0 g. The resulting solution was stirred at 0° C. for 2 hours at ambient temperature for an additional 90 minutes A white precipitate formed which was filtered off Solvent was removed from the filtrate under reduced pressure the residue chromatographed on a silica gel column eluting with 20% ethyl acetate/hexanes

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

Procedure: Scheme Vc, step A: 2-(4-Iodophenyl) propyl isopropylsulfonamide (1.5 g, 4.1 mmol), (phenylmethoxy)-N-prop-2-enylcarboxamide (0.94 g, 4.9 mmol, prepared in example 8), 9-BBN dimer (0.8 g, 3.28 mmol), [1,1′bis(diphenylphosphino)-ferrocene] dichloropalladium (II), PdCl2(dppf) (0.17 g, 0.2 mmol), 3N sodium hydroxide (3 mL), and pH=7 buffer: hydrogen peroxide (2:1, 15 mL) were combined in a manner analogous to the procedure described in example 6 to provide the intermediate title compound, N-{3-[4-(1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl]propyl}(phenylmethoxy)carboxamide, (1.74 g, 99%). Electron spray M.S. 431 (M*−H).

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

Procedure: N-[3-(4-Bromophenyl)propyl](phenylmethoxy)carboxamide (1.5 g, 4.3 mmol), (phenylmethoxy)-N-eth-2-enylcarboxamide (0.92 g, 5.17 mmol, prepared in example 8), 9-BBN-dimer (0.84 g, 3.45 mmol), [1,1′bis(diphenylphosphino)-ferrocene] dichloropalladium (11), PdCl2(dppf), (0.175 9, 0.22 mmol), 3N sodium hydroxide (3 mL), and pH=7 buffer hydrogen peroxide (2:1, 10 mL) were combined in a manner analogous to the procedure described in example 6 to provide the intermediate title compound, (phenylmethoxy)-N-[3-(4-{2-[(phenylmethoxy)carbonylamino]ethyl}phenyl)propyl]carboxamide, (0.68 g, 35%). Electron spray M.S. 447 (M*+H).

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

Procedure: Scheme IVc, step A: 1,4-Dibromobenzene (2 g, 8.5 mmol), (phenylmethoxy)-N-prop-2-enylcarboxamide (1.95 g, 10.1 mmol, prepared in example 8), 9-BBN-dimer (2.7 g, 11 mmol), [1,1′bis(diphenylphosphino)-ferrocene] dichloropalladium (II), PdCl2(dppf), (0.35 g, 0.42 mmol), 3N sodium hydroxide (3 mL), and pH=7 buffer hydrogen peroxide (2:1, 10 mL) were combined in a manner analogous to the procedure described in example 6 to provide the intermediate title compound, N-[3-(4-bromophenyl)propyl](phenylmethoxy)carboxamide, (1.6 g, 54%). Electron spray M.S. 348 (M*+2).

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

Procedure: Scheme IIIb, step A: 4-Bromo-2-fluorobenzonitrile (3 g, 15 mmol), (phenylmethoxy)-N-prop-2-enylcarboxamide (3.44 g, 18 mmol), 9-BBN dimer (2.93 g, 12 mmol), [1,1′bis(diphenylphosphino)ferrocene] dichloropalladium (II), PdCl2(dppf) (0.61 g, 0.75 mmol), 3N sodium hydroxide (10 mL), and pH=7 buffer: hydrogen peroxide (2:1, 20 mL) are combined in a manner analogous to the procedure described in example 6 to provide the intermediate title compound, N-[3-(4-cyano-3-fluorophenyl)propyl](phenylmethoxy)carboxamide, (4.18, 89%). Electron spray M.S. 313 (M*+H).

Conditions: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 250 mL single neck flask were placed allylamine (5 mL, 66.6 mmol) and triethylamine (11.1 mL, 80 mmol) in methylene chloride (80 mL). The mixture was cooled to −5° C. before being treated with benzylchloroformate (10 mL, 70 mmol) gradually. The reaction mixture was warmed up to RT while stirring overnight. The product was extracted with EtOAc and the organic layer was separated and washed twice with H2O, dried over anhydrous Na2SO4, filtered, and concentrated under reduced vacuum. The resulting oil was further purified via flash chromatography (Silica gel, isocratic) and eluting with a solvent of Hexanes/EtOAc 20% to provide the intermediate title compound, (phenylmethoxy)-N-prop-2-enylcarboxamide, (8.7 g, 68%) as oil. Electron spray M.S. 192 (M*+1). Into a 250 mL single neck flask were placed The reaction mixture was warmed up to RT The product was extracted with EtOAc the organic layer was separated washed twice with H2O dried over anhydrous Na2SO4 filtered concentrated under reduced vacuum The resulting oil was further purified via flash chromatography (Silica gel, isocratic) eluting with a solvent of Hexanes/EtOAc 20%