8-bromo-1,2,3,4-tetrahydro-1,4-benzodiazepin-5-one

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

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

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

Procedure: A mixture of 8-Bromo-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one (1.02 g, 4.23 mmol, 1 eq), cyclopropylboronic acid (480 mg, 5.5 mmol, 1.3 eq), tricyclohexylphosphine (121 mg, 0.42 mmol, 0.1 eq), Pd(OAc)2 (48 mg, 0.211 mmol, 0.05 eq), K3PO4 (3.2 g, 14.8 mmol, 3.5 eq) in Toluene (40 mL), water (4 mL), dioxane (10 mL), was degassed with argon and heated to 110 C for 15 hours. The reaction was cooled, diluted with ethyl acetate, washed sat. aq. Sodium bicarbonate solution, brine, and dried over mgso4, filtered, concentrated in vacuo and purified with flash chromatography on a silica gel column eluting with 50% ethyl acetate in hexanes to give 650 mg 8-Cyclopropyl-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one, 76%. was degassed with argon heated to 110 C for 15 hours The reaction was cooled diluted with ethyl acetate washed sat. aq. Sodium bicarbonate solution, brine dried over mgso4 filtered concentrated in vacuo purified with flash chromatography on a silica gel column eluting with 50% ethyl acetate in hexanes

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

Procedure: A mixture of 4-Bromo-2-fluoro-benzoic acid (500 mg, 2.28 mmol) and 5 mL Ethane-1,2-diamine was reacted in a sealed tube under argon with microwave irradiation at 150 C for 30 min. The reaction was cooled, diluted with methylene chloride (200 mL), and DMF (10 mL) to give a homogeneous solution. 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU), (1 g, 2.63 mmol, 1.1 eq.) was added, and the reaction stirred at room temperature for 2 hours. The reaction was then heated to 95 C for 15 hours, cooled, and 3 mL 5 N NaOH was added. The mixture was stirred at room temperature for 1 hour, the reaction was concentrated in vacuo, extracted with ethyl acetate 3×, the organic layers were dried and concentrated. The residue was purified by flash chromatography to give 150 mg of 8-Bromo-1,2,3,4-tetrahydro-benzo[e][1,4]diazepin-5-one, 27%. was reacted in a sealed tube under argon with microwave irradiation at 150 C for 30 min The reaction was cooled to give a homogeneous solution The reaction was then heated to 95 C for 15 hours cooled The mixture was stirred at room temperature for 1 hour the reaction was concentrated in vacuo extracted with ethyl acetate 3× the organic layers were dried concentrated The residue was purified by flash chromatography