OTBN is an advanced drug intermediate for - sartan group of drugs, such as candesartan, irbesartan, losartan, tasosartan, and valsartan, which are used for treatment of hypertension as well as for treatment of heart failures. OTBN is imported in huge quantities in India for manufacturing these drugs in bulk amounts. To curb the import dependency, and to promote local manufacturing, BARC has developed a cost-effective and industry- friendly process for synthesis of o-Tolylbenzonitrile (OTBN). It has been developed by utilizing cross-coupling methodologies to selectively heterocouple two chemically differentiated aromatic partners.

1. The process is based on the indigenously developed technology and locally available materials.
2. Low amount of waste with minimum environmental pollution.
3. Solvent recovery and reuse makes this process attractive, and economic.
4. Technical parameters: characterized using NMR, GC-MS; Purity >99% (GC-MS), melting point: 50-52 °C.

1. As an advanced drug intermediate for -sartan group of drugs, such as candesartan, irbesartan, losartan, tasosartan, and valsartan, which are used for treatment of hypertension as well as for treatment of heart failures?

BARC has developed a process for synthesis of o-Tolylbenzonitrile (OTBN), with high purity (>99%, GC-MS), suitable for use as a building block (intermediate) for anti-hypertensive -sartan group of drugs, such as candesartan, irbesartan, losartan, tasosartan, and valsartan.

INTRODUCTION :

OTBN is an advanced drug intermediate for -sartan group of drugs, such as candesartan, irbesartan, losartan, tasosartan, and valsartan, which are used for treatment of hypertension as well as for treatment of heart failures. OTBN is imported in huge quantities in India for manufacturing these drugs in bulk amounts. To curb the import dependency, and to promote local manufacturing, a suitable cost-effective, industry- friendly method needs to be developed. Herein, an economic route for the synthesis of OTBN has been developed, utilizing cross-coupling methodologies to selectively heterocouple two chemically differentiated aromatic partners. The synthetic method comprises of two industrially friendly steps utilizing organometallic reagents and innovative catalytic systems, which have been validated in multi-gram scale with high degree of repeatability. Solvent recovery and re-use makes this process highly economic and more competitive. The product can easily be purified at >99% (GC-MS) purity using column chromatography or distillation under reduced pressure.

1. The process is based on the indigenously developed technology and locally available materials.
2. The process is based on the indigenously developed technology and locally available materials.
3. The process generates very low amount of waste, with minimum environmental pollution.
4. Solvent recovery and reuse makes this process attractive, and economic.
5. Technical parameters: characterized using NMR, GC-MS; Purity >99% (GC-MS), Melting point: 50-52 °C.
6. Good market potential as an import substitute.
7. Can be manufactured at lower cost compared to the imported item.

1. As an advanced drug intermediate for sartan group of drugs, such as candesartan, irbesartan, losartan, tasosartan, and valsartanin, which are used for treatment of hypertension as well as for treatment of heart failures

RAW MATERIALS

1. All the raw materials required are available in the local market.

EQUIPMENTS

1. Temperature controlled (0-100 οC) chemical reactor with mechanical stirring, water condenser and facilities for dropwise addition of reagents under inert atmosphere-2 nos.
2. Argon gas cylinder
3. Vacuum pump with at least 5 mmHg pressure on pot.
4. Standard vacuum distillation unit with temperature range 50-200 °C.

SPACE

1. Factory shade of 200 sq. ft. area with the above facilities.

POWER

1. Single phase power connection.

MANPOWER

1. Chemist: 01, Technician and operator: 01