Phosphorus oxychloride → Benzodiazepine
Reaction equation
[N:1]1[NH:2][C:3](=O)[C:4](=O)[CH:5]=[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=12.P(Cl)(Cl)(Cl)=O>>[NH:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH:5]=[CH:4][CH:3]=[N:2]1Participants
Procedure
The title compound was prepared according to the procedures shown in the scheme below. Compound 5-chloroisatoic anhydride (A) was reacted with (R)-2-chlorophenylalanine to provide benzodiazepine-dione B based on procedures described in, for instance, Example 2. Reaction of benzodiazepine-dione B with para-methoxybenzyl chloride in the presence of base, according to procedures described in, for instance, Example 3, provided PMB-protected benzodiazepine-dione C. Conversion of benzodiazepine-dione C to imidoyl chloride D was accomplished using phosphorous oxychloride, based on procedures described in, for instance, Example 4. The substituted phenyl group was installed using Suzuki coupling, based on procedures described in, for instance, Example 7, to provide benzodiazepine E. The PMB protecting group was removed by reacting benzodiazepine E with AlCl3, based on procedures described in, for instance, Example 8, to provide benzodiazepine F. Methyl phenyl ether F was converted to phenol G using boron tribromide, based on procedures described in, for instance, Example 16.
Sources & evidence
- ORD record
- ord-753f3c291f4448798836797ed2e84f04
- Source dataset
- uspto-grants-2014_03
- Patent number
- US08673897B2
Reaction notes
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