Formyl Olanzepine.....N-demethyl-N-formyl olanzapine Impurity

 

N-demethyl-N-formyl olanzapine Impurity

2-methyl-4-(4-formyl-l-piperazinyl)-10H-thieno[2,3-b]- [l,5]benzodiazepine (Ν-demethyl-Ν-formylolanzapine) 

1-​Piperazinecarboxalde​hyde, 4-​(2-​methyl-​10H-​thieno[2,​3-​b]​[1,​5]​benzodiazepin-​4-​yl)​-

 CAS 639460-79-0

C₁₇ H₁₈ N₄ O S, 326.42

 

 

  1H NMR PREDICT

 

  13C NMR

COSY AND HMBC ABOVE

 PATENT

http://www.google.com/patents/US7329747

An alternative of the above process was suggested in WO 04/000847 and comprises converting the compound (2) into a “formyl-olanzapine precursor” of formula (4) by a reaction with a methyl formate, and converting the compound (4) into olanzapine by a reduction with a metal borohydride.

Example 1
N-Formyl Olanzapine (4)
In a 1000 ml flask, a mixture of 12.0 g of “des-methylpiperazine olanzapine precursor” (compound of formula (2)) hydrochloride and 40 ml of N-formyl piperazine in a mixture of 60 ml of dimethylsulfoxide and 60 ml of toluene was heated at reflux under a nitrogen atmosphere overnight. Progress was monitored by HPLC. After cooling to 40° C., 160 ml of water was added. The resulting mixture was cooled and stirred at 0° C. The solid material was isolated by filtration and washed with 2×40 ml of water. Wet solid was dried overnight at ambient conditions and subsequently at 40° C. under vacuum.
Isolated yield: 12.19 gram, Purity (HPLC): 91.6%
....................
.


.


///////////////////////////////////////

 http://www.google.co.in/patents/WO2005070939A1?cl=en

 Example 1 N-formyl olanzapine (4) In a 1000 ml flask, a mixture of 12.0 g of "des-methylpiperazine olanzapine precursor" (compound of formula (2)) hydrochloride and 40 ml of N-formyl piperazine in a mixture of 60 ml of dimethylsulfoxide and 60 ml of toluene was heated at reflux under a nitrogen atmosphere overnight. Progress was monitored by HPLC. After cooling to 40°C, 160 ml of water was added. The resulting mixture was cooled and stirred at 0°C. The solid material was isolated by filtration and washed with 2x 40 ml of water. Wet solid was dried overnight at ambient conditions and subsequently at 40°C under vacuum. Isolated yield : 12.19 gram , Purity (HPLC) : 91.6%
Example 2 Crystallization of the compound (4) 8.0 g of crude N-formyl olanzapine precursor (compound (4)) of a purity of about 89% (HPLC) was suspended in 50 ml of methanol and heated at 60°C for 3 hours. The hot suspension was allowed to cool to room temperature and was subsequently cooled to 5°C^"7 under stirring. The solid material was isolated by filtration, washed with 5 ml of cold methanol and 10 ml of cold diethyl ether and dried overnight at 40°C under vacuum. Yield : 3.97 g, purity 96.7 % (HPLC)


 ......................
http://www.google.co.in/patents/WO2004000847A1?cl=en
preparation of 2-rnethyl-4-(4-forrnyl-l-piperazinyl)-10H-thieno[2,3- b][l,5]-benzodiazepine (N-demethyl-N-formylolanzapine) of formula HI,

which process comprises reaction of 2-methyl-4-piperazin-l-yl- 10H-thiene-[2,3-b][l,5]-benzodiazepine (N-demethylolanzapine) of formula II

with ethyl formate. The reaction with ethyl formate is carried out as described above for the second variant of the first aspect of the invention, that is for the preparation of olanzapine by reaction of N-demethylolanzapine of formula II with ethyl formate and then reduction. The invention will be described in more detail with reference to the following, non-limiting examples, which should not be construed as the limitation of its scope. Example 1. N-Demethylolanzapine Preparation
A mixture of 4-amino-2-methyl-10H-thieno[2,3-b][l,5]benzo- diazepine hydrochloride (3 g, 11.3 mmol), piperazine (7 g, 81.4 mmol) in 15 ml of DMSO and 15 ml of toluene was heated to reflux under an inert gas atmosphere, with no access of moisture of the air. The reaction mixture was refiuxed for 2 h.
After completion of the reaction the reaction mixture was cooled in an ice-bath and 30 ml of distilled water was added. The mixture was stirred at 5°C for 1 h until completion of the formation of a precipitate. The light-yellow precipitate was filtered off, washed with water and dried in a vacuum desiccator over silica gel. 2.89 g (yield 85,7%) of N-Demethylolanzapine was obtained; m.p. 144.5°C.


................
OLANZEPINE IMPURITIES


.


.






http://www.synzeal.com/olanzepine_impurities.html

Olanzapine EP Impurity A

Cat No       : SZ-O110

CAS No     : 138564-59-7

Mol Wt      : 259.3

Mol Form : C12H9N3O2S

Olanzapine EP Impurity B

Cat No       : SZ-O104

CAS No     : 221176-49-4

Mol Wt      : 230.1

Mol Form : C12H10N2OS

Olanzapine EP Impurity C

Cat No       : SZ-O105

CAS No     : 719300-59-1

Mol Wt      : 397.4

Mol Form : C18H22Cl2N4S

Olanzapine EP Impurity D

Cat No       : SZ-O106

CAS No     : 174794-02-6

Mol Wt      : 328.4

Mol Form : C17H20N4OS

Olanzapine Lactam

Cat No       : SZ-O102

CAS No     : 1017241-34-7

Mol Wt      : 312.3

Mol Form : C17H20N4O2

Olanzapine Thiolactam

Cat No       : SZ-O103

CAS No     : 1017241-36-9

Mol Wt      : 328.4

Mol Form : C17H20N4OS

Olanzapine N-Formyl Impurity

Cat No       : SZ-O107

CAS No     : NA

Mol Wt      : 326.4

Mol Form : C17H18N4OS

Olanzapine N-Desmethyl

Cat No       : SZ-O108

CAS No     : 161696-76-0

Mol Wt      : 298.4

Mol Form : C16H18N4S

OLANZAPINE.....http://www.tlcpharmachem.com/tlc_item.php?upc=O-0115&li=le_21&sub=O

Olanzapine CAS No. 132539-06-1 M.F.: C17H20N4S M.W.: 312.44 O-011 Olanzapine-d3 CAS No. 132539-06-1(non-d) M.F.: C17H17N4SD3 M.W.: 315.46 O-012 Olanzapine N-oxide (Olanzapine Impurity D) CAS No. 174794-02-6 M.F.: C17H20N4S M.W.: 328.44 O-013 Olanzapine-d8 CAS No. 1093380-13-2 M.F.: C17H12N4SD8 M.W.: 320.49 O-014 N-Desmethyl Olanzapine-d8 CAS No.  M.F.: C16H10N4SD8 M.W.: 306.46 O-015 Desmethyl Olanzapine Impurity (N-Desmethyl Olanzapine) CAS No. 161696-76-0 M.F.: C16H18N4S M.W.: 298.41 O-016 Olanzapine Amide (Olanzapine Impurity B) CAS No. 221176-49-4 M.F.: C12H10N2OS M.W.: 230.29 O-017 Olanzapine Related Compound HCl CAS No. 138564-60-0 M.F.: C12H11N3S. HCl M.W.: 229.31 36.46 O-018 Olanzapine Ketolactam CAS No. 1017241-34-7 M.F.: C17H20N4O2 M.W.: 312.37 O-019 Olanzapine Ketothiolactam CAS No. 1017241-36-9 M.F.: C17H20N4OS M.W.: 328.44 O-0110 Olanzapine Impurity C CAS No. 719300-59-1 M.F.: C18H22ClN4S Cl M.W.: 361.92 35.45 O-0113 Olanzapine Impurity A CAS No. 138564-59-7 M.F.: C12H9N3O2S M.W.: 259.29 O-0114 Olanzapine Thiohydroxymethylidene (Hydroxymethylidene Thione) CAS No. 1320360-86-8 M.F.: C15H18N4OS M.W.: 302.40 O-0116 Olanzapine Ketothiolactam S-oxide CAS No. N/A M.F.: C17H20N4O2S2 M.W.: 344.44 O-0117 Olanzapine Amino Impurity CAS No. 873895-41-1 M.F.: C12H11N3S M.W.: 229.31 O-0118 Olanzapine Ring-opening Impurity CAS No. 138564-61-1 M.F.: C17H22N4OS M.W.: 330.46 O-0119 N-Desmethyl N-Ethyl Olanzapine CAS No. 1355034-54-6 M.F.: C18H22N4S M.W.: 326.47 O-01110 Olanzapine impurity (1-(5'-Methylthiophen-2'-yl)-1,3-dihydrobenzoimidazol-2-one) CAS No.  M.F.: C12H10N2OS M.W.: 230.29 O-01111 4-Fluoro Olanzapine CAS No.  M.F.: C17H19FN4S M.W.: 330.43 O-01112 Olanzapine Impurity K CAS No. N/A M.F.: C6H6N2S M.W.: 138.19 O-0120

FRANCE

Republican march, Place de la République, Paris.

The St. Bartholomew's Day massacre (1572) was the climax of theFrench Wars of Religion, which were brought to an end by the Edict of Nantes (1598).

One of the Lascaux paintings: a horse – Dordogne, approximately 18,000 BC

With Clovis' conversion to Catholicism in 498, theFrankish monarchy, electiveand secular until then, became hereditary and ofdivine right.



Frankish expansion from 481 to 843/870.

The Storming of the Bastille on 14 July 1789 was the starting event of theFrench Revolution.

Louis XIV, the "sun king" was the absolute monarch of France and made France the leading European power.

Napoleon, Emperor of the French, and his Grande Armée built a vast Empire across Europe. He helped spread the French revolutionary ideals and his legal reforms had a major influence worldwide.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

COCK WILL TEACH YOU NMR

COCK SAYS MOM CAN TEACH YOU NMR

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com