A preparation method for alprazolam intermediate benzodiazepine thioketones,
Concrete steps are as follows:
1. acylation reaction
In reaction flask, add the chloro-benzophenone (M of 2-amino-5-2) 250g (1.08mol), hexanaphthene 1750g, stir and it be warming up to 60 DEG C, drip and add chloroacetyl chloride 160g(1.36mol), then it is warming up to 81 DEG C, backflow 4h(has hydrogenchloride to release in reacting). React complete and it is cooled to 10 DEG C, precipitate out pale yellow crystals. Filtration, drying, obtain pale yellow crystals M3320g, product rate 95%, HPLC content > 98%, mp117��119 DEG C.
2. cyclization
Reaction flask adds M3320g (1.03mol), 3200g dehydrated alcohol, 260g urotropine (i.e. vulkacit H), heated and stirred to 50 DEG C, adds bicarbonate of ammonia 142g(1.80mol), bicarbonate of ammonia gradation in 3h on average adds. 40 DEG C of reaction 6h, HPLC tracing detection are complete to raw material reaction. Evaporated under reduced pressure, with 40 DEG C of hot water making beating. Filter (using 95v% washing with alcohol), drying, obtain pale yellow crystals M4230g, product rate 82%, HPLC content > 90%, mp212��215 DEG C.
3. vulcanization reaction
Nitrogen protection, in dry reaction bottle, adds toluene 975g, triethylamine 160g, thiophosphoric anhydride 204g(0.92mol), after stirring clarification, add M4230g(0.85mol), it is warming up to 75 DEG C of reaction 8h. Reacting complete and be cooled to room temperature, filtration, drying, obtain pale yellow crystals M5195g, product rate 80%, HPLC content > 94%, mp234��237 DEG C.

By the M that above-mentioned preparation method obtains5Crude product is refined, and comprises the steps:
Normal temperature adds the N of 1 times of crude product weight, and dinethylformamide dissolves crude product, elimination residue. Add water recrystallization, makes N, dinethylformamide: the mass ratio of water is 1:1, treats M5After complete recrystallization, take out filter, after dry, obtain fine work 175g, refining rate 90%. Fine work is light yellow or class yellow crystalline powder, HPLC content >=98.5%, it is known that foreign matter content��1.0%, fusing point 238��242 DEG C, weight loss on drying��0.5%, and burn residual��0.2%.