OLANZEPINE KEY INT........N-desmethyl olanzapine

N-desmethyl olanzapine



http://www.google.com.tr/patents/US20050272720



EXAMPLE 5 N-Methylation of N-desmethyl olanzapine and isolation of olanzapine as the acetate salt

Reaction scheme:

In a 250 ml flask, equipped with a magnetic stirrer 3.0 g of N-desmethyl olanzapine was dissolved in 30 ml of DMSO. Then, 0.852 g of 37% formaldehyde and 0.492 g of formic acid were added and the resulting mixture was heated at 80° C. for 2 hours. After cooling to room temperature, 120 ml of ethyl acetate and 120 ml of water were added. The organic layer was washed twice with 100 ml water and once with 100 ml saturated aqueous NaCl, dried over Na₂SO₄, and concentrated at reduced pressure to a volume of about 25 ml. Then, 1.0 ml acetic acid was added, and the resulting mixture was stirred for 3 days at 4° C. The product (light yellow) was isolated by filtration, and washed with 5 ml of diethyl ether, and dried subsequently at ambient conditions. Isolated yield: 1.19 g (58%) (=. batch.01).

Then, drying of 0.40 g of batch.01 in vacuum at 70° C. for 2 days yielded olanzapine free base quantitatively. Data: ¹H-NMR and XRPD confirm Olanzapine Form I.

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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.

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OLANZEPINE IMPURITY

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.

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Development of a simple and stability-indicating RP-HPLC method for determining olanzapine and related impurities generated in the preparative process

Development of a simple and stability-indicating RP-HPLC method for determining olanzapine and related impurities generated in the preparative process

Daoping Cui,^a   Yueqing Li,^a   Mingming Lian,^a   Feng Yang^b and  Qingwei Meng*^a  

*

Corresponding authors

^a

State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, No. 2 Linggong Road, Ganjingzi District, Dalian, P. R. China
E-mail: mengqw@dlut.edu.cn

^b

Merro Pharmaceutical Companies, No. 9 Yingsheng Road, Ganjingzi District, Dalian, P. R. China

Analyst, 2011,136, 3149-3156

DOI: 10.1039/C1AN15155Jhttp://pubs.rsc.org/en/content/articlelanding/2011/an/c1an15155j#!divAbstract

A simple and stability-indicating reverse phase high performance liquid chromatographic (RP-HPLC) method was developed and validated for the determination of olanzapine (OLN) and related impurities in bulk drugs. Eight impurities were characterized respectively, and particularly a new process impurity from OLN synthesis was structurally confirmed as 1-(5-methylthionphen-2-yl)-1H-benzimidazol-2(3H)-one (Imp-7) by X-ray single crystal diffraction,MS, ¹H NMR, ¹³C NMR and HSQC. A mechanism of formation pathway for Imp-7 was proposed. Optimum separation for OLN and eight related impurities was carried out on an Agilent Octyldecyl silica column (TC-C₁₈, 4.6 mm × 250 mm, 5 μm) using a gradient HPLC method. The method was validated with respect to specificity, linearity, accuracy, precision, LOD and LOQ. Regression analysis showed good correlation (r² > 0.9985) between the investigated component concentrations and their peak areas within the test ranges for OLN and eight impurities. The repeatability and intermediate precision, expressed as RSD, were less than 1.74%. The proposed stability-indicating method was suitable for routine quality control anddrug analysis of OLN in bulk drugs.

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a State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of Technology, No. 2 Linggong Road, Ganjingzi District, Dalian, Liaoning Province, 116024, P. R. China. E-mail: mengqw@dlut.edu.cn














b Merro Pharmaceutical Companies, No. 9 Yingsheng Road, Ganjingzi District, Dalian, Liaoning Province, 116036, P. R. China

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

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ACETYL IMPURITY OF OLANZEPINE

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