Midazolam → HCID 131728283, compound

HRID 502496Notes

Reaction equation

HRID 502496 reaction equation
C[C:2]1[N:6]2[C:7]3[CH:8]=[CH:9][C:10]([Cl:23])=[CH:11][C:12]=3[C:13]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=3[F:22])=[N:14][CH2:15][C:5]2=C[N:3]=1.NCC1CN=C(C2C=CC=CC=2F)C2C=C(Cl)C=CC=2N1.C(O[C:49](=[O:51])[CH3:50])(=O)C>ClCCl>[C:49]([NH:3][CH:2]1[CH2:15][N:14]=[C:13]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=2[F:22])[C:12]2[CH:11]=[C:10]([Cl:23])[CH:9]=[CH:8][C:7]=2[N:6]1[CH3:5])(=[O:51])[CH3:50]

Participants

5

Reactant 3

HCID 4192MidazolamHCID 7918Acetic AnhydrideHCID 155632447-Chloro-5-(2-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine-2-methanamine

Product 1

HCID 131728283HCID 131728283, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

U.S Pat. No. 4,280,957 (hereinafter the '957 patent) describes a synthetic process for preparing midazolam, which is depicted in Scheme 2 below. This process includes reacting 2-aminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-bezodiazepine (II) with acetic anhydride in dichloromethane to produce 2-acetamido-methyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-bezodiazepine (III). The latter is heated with polyphosphoric acid at 150° C. to produce 8-chloro-6-(2-fluorophenyl)-3a,4-dihydro-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine of formula (IV), which is purified by column chromatography. Compound IV is then mixed with toluene and manganese dioxide and heated to reflux to afford midazolam base, which is crystallized from ether to yield a product with mp of 152-154° C.

Sources & evidence

ORD record
ord-53aa36d11fdc45dea0060dccf187ab25
Source dataset
uspto-grants-2010_08
Patent number
US07776852B2

Reaction notes

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