4-amino-2-prop-2-enoxybenzonitrile

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

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

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

Procedure: To a solution of 10B (1.9 g, 10.9 mmol) in anhydrous CH2Cl2 (16 mL) cooled at 0° C. was added 1 N aqueous NaOH solution (16.4 mL, 16.4 mmol), followed by pivaloyl chloride (1.9 mL, 15.3 mmol). After the addition, the reaction mixture was stirred at 0° C. for 2 h, then concentrated under reduced pressure to remove most of the CH2Cl2 solvent. The remaining residue was diluted with water, and the resulting precipitate collected by filtration, washed with water, hexane, and dried under vacuum to furnish the title compound as a light brown solid (2.6 g). After the addition concentrated under reduced pressure to remove most of the CH2Cl2 solvent The remaining residue was diluted with water the resulting precipitate collected by filtration washed with water, hexane dried under vacuum

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

Procedure: The title compound (1.70 g) as a light yellow solid was prepared from compound 10A (2.04 g, 10 mmol) by procedures analogous to those described in Experiment 6C.

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

Procedure: To a solution of 10B (1.9 g, 10.9 mmol) in anhydrous CH2Cl2 (16 mL) cooled at 0° C. was added 1 N aqueous NaOH solution (16.4 mL, 16.4 mmol), followed by pivaloyl chloride (1.9 mL, 15.3 mmol). After the addition, the reaction mixture was stirred at 0° C. for 2 h, then concentrated under reduced pressure to remove most of the CH2Cl2 solvent. The remaining residue was diluted with water, and the resulting precipitate collected by filtration, washed with water, hexane, and dried under vacuum to furnish the title compound as a light brown solid (2.6 g). After the addition concentrated under reduced pressure to remove most of the CH2Cl2 solvent The remaining residue was diluted with water the resulting precipitate collected by filtration washed with water, hexane dried under vacuum

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

Procedure: To a solution of 10B (1.9 g, 10.9 mmol) in anhydrous CH2Cl2 (16 mL) cooled at 0° C. was added 1 N aqueous NaOH solution (16.4 mL, 16.4 mmol), followed by pivaloyl chloride (1.9 mL, 15.3 mmol). After the addition, the reaction mixture was stirred at 0° C. for 2 h, then concentrated under reduced pressure to remove most of the CH2Cl2 solvent. The remaining residue was diluted with water, and the resulting precipitate collected by filtration, washed with water, hexane, and dried under vacuum to furnish the title compound as a light brown solid (2.6 g). After the addition concentrated under reduced pressure to remove most of the CH2Cl2 solvent The remaining residue was diluted with water the resulting precipitate collected by filtration washed with water, hexane dried under vacuum

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

Procedure: The title compound (1.70 g) as a light yellow solid was prepared from compound 10A (2.04 g, 10 mmol) by procedures analogous to those described in Experiment 6C.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(allyloxy)-4-aminobenzonitrile (Preparation D, 168 mg, 0.963 mmol), and N-allyl-2-chloro-7-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (Preparation Ua, 204 mg, 0.642 mmol) in N-Methyl-2-pyrrolidinone (5135 μL) was added H2SO4 (54.7 μL, 1.027 mmol). The mixture was stirred at 100° C. overnight. The crude reaction mixture was purified by PREP HPLC: (50×250 mm HPLC XTerra C18.15 to 100% A:B over 40 min, 3 min at 100% B (A is 90:10:0.1 water:MeOH:TFA; B is 90:10:0.1 MeOH:water:TFA)). The appropriate fractions were concentrated in vacuo to afford 4-(4-(allylamino)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-ylamino)-2-(allyloxy)benzonitrile (74 mg, 25% yield). LC-MS (M+H)+=456.1. The crude reaction mixture was purified by PREP HPLC to 100% A:B over 40 min 3 min The appropriate fractions were concentrated in vacuo

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(allyloxy)-4-aminobenzonitrile (Preparation D, 168 mg, 0.963 mmol), and N-allyl-2-chloro-7-(4-fluorophenyl)-7-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-amine (Preparation Ua, 204 mg, 0.642 mmol) in N-Methyl-2-pyrrolidinone (5135 μL) was added H2SO4 (54.7 μL, 1.027 mmol). The mixture was stirred at 100° C. overnight. The crude reaction mixture was purified by PREP HPLC: (50×250 mm HPLC XTerra C18.15 to 100% A:B over 40 min, 3 min at 100% B (A is 90:10:0.1 water:MeOH:TFA; B is 90:10:0.1 MeOH:water:TFA)). The appropriate fractions were concentrated in vacuo to afford 4-(4-(allylamino)-7-(4-fluorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-ylamino)-2-(allyloxy)benzonitrile (74 mg, 25% yield). LC-MS (M+H)+=456.1. The crude reaction mixture was purified by PREP HPLC to 100% A:B over 40 min 3 min The appropriate fractions were concentrated in vacuo

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Iron powder-325 mesh (5.7 g, 98.0 mmol) was taken in a round bottom flask charged with a mixture of 2-(allyloxy)-4-nitrobenzonitrile (4.0 g, 19.6 mmol), absolute methanol (40 mL), water (8 mL) and ammonium chloride (5.2 g, 98 mmol). A water-cooled reflux condenser was attached to the flask and the heterogeneous mixture was heated to 65° C. with vigorous stirring for 50 min. The reaction mixture was filtered, and washed with methanol. The solvent was removed in vacuo. EtOAc was added to the residue, and the solution was washed with water and brine. The organic layer was dried over MgSO4, filtered, and concentrated to afford 2-(allyloxy)-4-aminobenzonitrile (3.2 g, 94% yield) as a light-brown solid. LC-MS (M+H)+=175.2 1H NMR (400 MHz, CDCl3) δ ppm 7.29 (d, 1H, J=8.4 Hz), 6.22 (dd, 1H, J=2.0, 8.4 Hz), 6.14 (s, 1H), 6.07-5.98 (m, 1H), 5.48 (dd, 1H, J=1.6, 3.2 Hz), 5.44 (dd, 1H, J=1.6, 3.2 Hz), 4.59 (d, 2H, J=1.6 Hz). reflux condenser The reaction mixture was filtered washed with methanol The solvent was removed in vacuo EtOAc was added to the residue the solution was washed with water and brine The organic layer was dried over MgSO4 filtered concentrated

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

Procedure: The title compound (1.70 g) as a light yellow solid was prepared from compound 10A (2.04 g, 10 mmol) by procedures analogous to those described in Experiment 6C.

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

Procedure: To a solution of 10B (1.9 g, 10.9 mmol) in anhydrous CH2Cl2 (16 mL) cooled at 0° C. was added 1 N aqueous NaOH solution (16.4 mL, 16.4 mmol), followed by pivaloyl chloride (1.9 mL, 15.3 mmol). After the addition, the reaction mixture was stirred at 0° C. for 2 h, then concentrated under reduced pressure to remove most of the CH2Cl2 solvent. The remaining residue was diluted with water, and the resulting precipitate collected by filtration, washed with water, hexane, and dried under vacuum to furnish the title compound as a light brown solid (2.6 g). After the addition concentrated under reduced pressure to remove most of the CH2Cl2 solvent The remaining residue was diluted with water the resulting precipitate collected by filtration washed with water, hexane dried under vacuum