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Flunitrazepam

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Reaction Stages Notes Yield

1 1.1 C:MeOH Reactants: 2, Catalysts: 1, Stages: 1

References

Industrial method for producing and purifying pharmaceutical quality flunitrazepam

By Autin, Jean Marie

From Fr. Demande, 2529203, 30 Dec 1983

CASREACT ®: Copyright © 2011 American Chemical Society. All Rights Reserved. CASREACT contains reactions from CAS and from: ZIC/VINITI database (1974-1999) provided by InfoChem; INPI data prior to 1986;

Biotransformations database compiled under the direction of Professor Dr. Klaus Kieslich; organic reactions, portions copyright 1996-2006 John Wiley & Sons, Ltd., John Wiley and Sons, Inc., Organic Reactions Inc., and Organic Synthesis Inc. Reproduced under license. All Rights Reserved.

2 1.1 R:HNO3, R:H2SO4 Reactants: 1, Reagents: 2, Stages: 1

References

Industrial method for producing and purifying pharmaceutical quality flunitrazepam

By Autin, Jean Marie

From Fr. Demande, 2529203, 30 Dec 1983

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3 1.1 S:CHCl3

Reactants: 2, Solvents: 1, Stages:

1

References

Synthesis of 7-chloro-5-(4-chlorophenyl)-1-methyl-1,3-dihydro-1,4-benzodiazepin-2-one

By Vejdelek, Zdenek et al

From Collection of Czechoslovak Chemical Communications, 50(5), 1064-9; 1985

4 1.1 R:N2H4, S:MeOH Reactants: 1, Reagents: 1, Solvents: 1, Stages: 1

References

Synthesis of 7-chloro-5-(4-chlorophenyl)-1-methyl-1,3-dihydro-1,4-benzodiazepin-2-one

By Vejdelek, Zdenek et al

From Collection of Czechoslovak Chemical Communications, 50(5), 1064-9; 1985

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References

Industrial method for producing and purifying pharmaceutical quality flunitrazepam By Autin, Jean Marie

From Fr. Demande (1983), FR 2529203 A1 19831230, Language: French, Database:

CAPLUS

Pharmaceutical grade flunitrazepam (I) was prepd. by nitration of

5-o-fluorophenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one followed by N-methylation of the resulting nitro compd. I is recrystd. from MeCN and MeOH, has a m.p. 170-72° and contains

<0.5% of the starting nitro compd.

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Photobinding of flunitrazepam and its major photodecomposition product N-desmethylflunitrazepam

By Busker, Ruud W.; Beijersbergen van Henegouwen, Gerard M. J.; Kwee, Brigitta M. C.;

Winkens, Jos H. M.

From International Journal of Pharmaceutics (1987), 36(2-3), 113-20. Language: English, Database: CAPLUS,DOI:10.1016/0378-5173(87)90145-1

Photodecompn. of flunitrazepam (I) and its photolabeling to human serum albumin (HSA) under oxygen-rich and –poor conditions were studied. The kinetics of both photodecompn. and photolabeling in oxygen-flushed solns. Correspond completely with those found under normal aerobic conditions, as usually applied in photoaffinity labeling (PAL) of benzodiazepine receptor sites. This correspondence also holds for the photoproducts found. Nitroredn.

Products photochem. formed in the absence of oxygen, appeared not likely to contribute in PAL, in contrast to what has been suggested earlier. I photodecomposes up to about 55% into N-desmethylflunitrazepam (D-I) under aerobic conditions. In this case photolabeling to HSA proceeds far more efficiently, and results in twice as much covalent binding, as in an oxygen-poor environment. D-I also photobinds to HSA to an extent comparable to that of I.

The results may in part explain the low percentage (20-25%) of photolabeled sites in PAL with [methyl-3H]I by loss of label by photo de compn. of I into D-I photobinding of (unlabeled) D-I leading to a decrease of receptor sites available for labeled I and

destruction of receptor sites by singlet oxygen produced by photoexcited nitrobenzodiazepine.

Synthesis of 7-chloro-5-(4-chlorophenyl)-1-methyl-1,3-dihydro-1,4-benzodiazepin-2-one By Vejdelek, Zdenek; Polivka, Zdenek; Protiva, Miroslav

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From Collection of Czechoslovak Chemical Communications (1985), 50(5), 1064-9. Language:

English, Database:CAPLUS, DOI:10.1135/cccc19851064

The title compd. I was prepd. from 5-chloro-3-(4-chlorophenyl)-2,1-benzisoxazole via new intermediates 4,2-Cl(p-ClC6H4CO)C6H3NRMe (R = COCH2Cl, phthalimidoacetyl). Addnl.

obtained was the o-fluorophenyl deriv. of I.