civentichem india presentation - 2012.ppt

Global operations in the USA and India with project management,IP control and local solutions at our USA headquarters

CiVentiChem (India) Private Limited

(Formerly Known as Indus BioSciences Private Limited)

1


• History• Business Overview• Services and Capabilities• Management Experience and Chemistry

Expertise• Chemistry Specialties & Capabilities• Bulk Projects Performed in Plant• Chemistry Experience

– Examples in Med. Chem & P R&D– Proprietary Building Blocks

• Facilities

2

Highlights of Presentation


History• 1994 - Founded in RTP, North Carolina• 1999 – Expanded to Larger Laboratory• 2000 – Reached 12 Scientists at USA• 2001 – R&D Laboratories Opened in India with

5 Chemists• 2009 – Launch of our Plant in Hyderabad,

India• 2011 – cGMP Synthesis lab in RTP, NC, USA

3


Business Overview• HQ: RTP, North Carolina• Services: Chemistry

– Discovery & Synthetic Chemistry, Process Development, Manufacturing & Analytical Services

• People: 80 Experienced Scientists & Admin• Facilities: USA and India

– RTP, North Carolina and Hyderabad, India– 50,000 Sq Ft Total Technical Facilities

• Customers: Around 150– including 10 of world Top 20 Pharma; 45 Biotechnology

Companies.• Integrated Management Systems

– ISO-9001-2008 (QMS), 14001-2004 (EMS) and 18001-2007 (OSHA)

4


BiologicalTarget

Screening Hits LaunchClinicalLeadsDrug

candidatePre -

clinical

ScreeningCompounds

CustomSynthesis

ParallelSynthesis

MedicinalChemistry

ManufacturingPilotPlant

ProcessScale -up

AssociatedChemistry

Peakdale Molecular Collaborators

-

BiologicalTarget

Screening Hits LaunchClinicalLeadsDrug

candidate

Pre -clinical

ScreeningCompounds

CustomSynthesis

ParallelSynthesis

MedicinalChemistry

ManufacturingPilotPlant

ProcessScale -up

AssociatedChemistry

CiVentiChem USA & India

CiVentiChem India

-

Our Role in Drug Development

5

DEVELOPMENT CHEMISTRY

•Rapid Initial Scale-up to first Kg•Process Research & Development•Feasibility Studies•Pilot Development Manufacture•Manufacture Intermediatess & APIs•cGMP & Non-GMP Protocols

RESEARCH CHEMISTRY

•Medicinal Chemistry•Focused Libraries•Reference Standards & Metabolites•Lead Compounds & NCEs•Lead Optimization•Intermediates and Building Blocks available and in-stock

PRODUCTION CHEMISTRY

•Pilot Development Manufacture

•Process Research & Development

•Contract Manufacturing •Manufacture Intermediates & APIs


Global Advantages

Flexibility of Choice… USA or India or BOTH !!

• Project Type• Deadline• Output Scale or Volume• Research Requirements• Expertise Requirements• Communication and Project Control• Lowest Cost

6


Business Overview - Clients

• No. of clients – 150• No. of Pharma Clients – 10 (from world

top 20 Pharma Companies)• No. of Biotech Clients – 10 +• No. of Catalogue Companies – 5 +• No. of Fine Chemical Companies – 10

+

7


Services and Capabilities

8


Research Chemistry Services

• Medicinal Chemistry• Synthesis of Focused Libraries &

Analogues• Synthesis of Reference Standards &

Metabolites• Synthesis of Lead Compounds & NCEs• Lead Optimization & Parallel Synthesis• Novel Template Molecules Ready for

Purchase9


Development/Manufacturing Services

• Rapid Initial Scale-up to 1st Kilogram• Route Scouting • Process Development & Optimization• Manufacture of Intermediates• API ready starting materials

10


Management Experience

11


Management Team

12

Bhaskar Venepalli, Ph. DBhaskar Venepalli, Ph. DChief Executive OfficerChief Executive Officer

Professional ExperienceProfessional Experience

25 + Years experience in fine chemicals

including 13 Yrs experience in R&D, new

product development & Business

Management at Eastman Kodak-Eastman

Chemical Company

Expertise in CRAMS & Fine Chemicals

Founder of Civentichem in 1994 in USA

EducationEducation

Ph.D. from Osmania University,

Hyderabad (IND)

Post Doctoral Research at University of

Southampton (England) & Rockefeller

University, New York, (USA)

Vasu (Srinivas) Vasu (Srinivas) Chittineni, Ph. DChittineni, Ph. D

Chief Technical OfficerChief Technical Officer


20 + Years experience in synthetic

organic chemistry

Expertise in Complex Organic

Syntheses, Chiral & Carbohydrate

Chemistry

Co founder of Civentichem in 1994

EducationEducation

Ph.D. from Kakatiya University (IICT,

Hyderabad, INDIA)

Post Doctoral Research at Duke

University , NC, USA


Management Team

13

Venkataiah Sunku, Ph. DVenkataiah Sunku, Ph. DManaging DirectorManaging Director


30 + Years experience in pharma

including 8 Yrs experience as Director

R&D at Aurobindo Pharma (India)

Expertise in Process Development &

Plant Scale operations

Developed processes for 22 bulk drugs

& Transferred to Mfg Plants

EducationEducation

Ph.D. in Chemistry from Osmania

University, Hyderabad (INDIA).

6 Publications & Patents

Venu (Venugopal) Venu (Venugopal) Veeramaneni, Ph. DVeeramaneni, Ph. D

Head R&D and BD&PMHead R&D and BD&PM


18 Years experience in Drug Discovery

(Medicinal &Synthetic Organic

Chemistry. Including 11 yrs at Dr.

Reddy’s Discovery Research.

Expertise in Synthesis of NME’s &

Complex Organic Syntheses

EducationEducation

Ph.D. in Chemistry from JNTUniversity

(DRF, Hyderabad, INDIA)

25 Publications, Patents &

Presentations


Research Team @ Civentichem India

14

Hari Prasad Chittineni, Ph.D.Hari Prasad Chittineni, Ph.D.Section Head, Process DevelopmentSection Head, Process Development

14 Yrs Experience in Carbohydrate, Heterocyclic Chemistry including 4 Yrs in AVRA Synthesis Expertise in Process DevelopmentM.Sc. From Osmania UniversityPh.D. from JNT University 7 Publications & Patents

Venkat Laxman Rao Cilamkoti, Ph.D.Venkat Laxman Rao Cilamkoti, Ph.D.Section Head, Medicinal ChemistrySection Head, Medicinal Chemistry

16 Yrs experience in Multi Step Organic Synthesis including 8 Yrs in Dr Reddy’s Discovery Research Expertise in Medicinal & Small scale ChemistryM.Sc. From Osmania UniversityPh.D. from Osaka University, Japan 9 Publications & Patents

Vineel, Vineel, Ph.DPh.D

Group Leader

5 Yrs Exp in Sugar &

Chiral Chemistry.

Ph.D. from JUNTU

MamathaMamathaGroup Leader

8 Yrs Exp in Azaindole & Indazole Chemistry

M.Sc. from Osmania University

GopalGopal Group Leader

8 Yrs Exp in Process &

Scale Up Chemistry


ShyamShyamGroup Leader

8 Yrs Exp in Med.

Chem. & Small Scale


RC SekarRC SekarGroup Leader

8 Yrs Exp in Med.

Chem. & Small Scale


RajithaRajithaGroup Leader

8 Yrs Exp in New

Building Blocks



Research Team @ Civentichem India


Chemistry Expertise & Performance Matrix

17


• Sugar Molecules

• Chiral Catalysts and Reagents

• Reagents for peptide formation

• Novel Hetero cyclic compounds for supporting all the

stages in drug discovery.

• Pyrazoles, Isoxazole, Oxazoles, Pyrazines, Pyridazines,

Pyrimidines, Pyrrolopyrimidine, Azaindoles, Indazoles,

Piperidinopyrimidines and Heterocycles having Spiro

group

• Chiral Binaphthols & Boronic Acids18

Chemistry Specialties


• General Reactions - mg to Kg scale• Grignard Reactions – Up to 50 kg of Mg charge• Bromination – mg to multi Kg scale•Hydrogenation Reactions – 350L SS, 30 kg/cm²•Transition Metal Reactions

• Suzuki coupling (0.5Kg, 1Kg to 25Kg Scale)

• Buchwald-Hartwig Coupling (5g & 500g Scale)• Negishi coupling (150g & 250g)•Sonogashira reaction (1Kg Scale)• Stille coupling (10g Scale)

• Enzymatic Resolutions • Reactions in Aqueous medium • Phosgenations using triphosgene

Chemistry Capabilities


Bulk Projects Performed in PlantS.No. Project Code Quantity No. of

StepsMonth of

completionRemarks/Key Chemistries

1 IB-205/151 45Kg 2 Oct, 2009 Iodination & amide formation

2 IB-205/284 120Kg 2 Nov, 2009 Indole Acylation

3 IB-150/011 425Kg & 415Kg

4 Jan & Oct 2010

Methylsulfonation & chlorination

4 IB-111/280 15Kg & 27Kg

3 Jan, 2010 Bromination & Phosphonate Chemistry

5 IB-111/291 15Kg & 27Kg

3 Jan, 2010 Bromination & Phosphonate Chemistry

6 IB-150/214 5Kg & 7Kg 7 Feb & Nov 2010

Cyclopropanation & Protection of Amine

7 IB-206/263 10Kg 1 Feb, 2010 Hydroxymethylation

8 IB-080/319 6Kg & 12Kg

2 March, 2010 Formyl pyrazoles



StepsMonth of


9 IB-206/320 21Kg/ 35Kg

4 March & July 2010

Amino acid Chemistry

10 IB-323/282 5Kg/30Kg 10 April & Nov 2010

Benzofuran formation, Suzuki coupling & Reduction

11 IB-323/086 7Kg 5 April 2010 Azaindole Chemistry & Catalytic hydrogenation

12 IB-206/263 10Kg/ 100Kg

1 April & june 2010

Hydroxymethylation

13 IB-313/275 3X100Kg 1 3 Times in 2010

Preparation Phase Transfer Catalyst

14 IB-150/333 15Kg 2 June, 2010 Nitration & etherification

15 IB-213/338 75Kg 2 June, 2010 Cyclopropanation

16 IB-150/014 24Kg 9 Sept, 2010 Nitration, Reduction and Migration



StepsMonth of


17 IB-080/293 10Kg 7 Oct, 2010 Azaindole Chemistry, Nitration & Bromination

18 IB-266/267 45Kg 3 Oct, 2010 Bromination & Selective Reduction

19 IB-036/206 10Kg / 100Kg

4 Oct, 2010 Grignard Reaction

20 IB-372/266 5Kg , 35Kg & 35Kg

2 Dec, 2010 & Feb, 2011

Bromination & Thiazole formation

21 BAL-PH 186Kg 2 Jan, 2011 Critical Reduction

22 IB-398/404 10Kg 3 Feb, 2011 Phosphonate Chemistry

23 IB-079/176 35Kg 1 Feb, 2011 Pyrazole formation

24 IB-373/399 48Kg 1 Feb, 2011 Cyclization



StepsMonth of


25 IB-416-205-3595

76Kg 3 April, 2011 Cyclization

26 IB-426-427-025

60Kg 4 June, 2011 Modified Reduction method to avoid expensive Pd

Charcoal

27 IB-147-150-3988

60Kg 5 July, 2011 Synthesized Starting Material instead of buying expensive

KSM

28 IB-455-150-5025

16Kg 4 July, 2011 Synthesized Starting Material instead of buying expensive

KSM

29 IB-407-150-5628

45Kg 10 July, 2011 Benzofuran formation, Suzuki coupling & Reduction

30 IB-232-450-4062

6Kg 5 July, 2011 Target is Very Useful KSM for Anti Viral APIs. And process

is performed in water


Bulk Projects Performed in PlantS.No.

Project Code

Quantity

No. of

Steps

Month of completio

n

Remarks/Key Chemistries

31CVI-429-428-7024

30Kg 1 August, 2011

Salt preparation as per client’s typical specifications

32CVI-476-428-092

30Kg 1 August, 2011


33CVI-431-428-7026

15Kg 1 August, 2011


34CVI-431-428-7025

15Kg 1 August, 2011


35IB-471-472-

088

10Kg & 25Kg

3 August, 2011 & Jan 2012

Handling of use amount of TFA (which is minimized to 30%)

36 CVI-432-150-5025

40Kg 5 November, 2011

Synthesized Starting Material instead of

buying expensive KSM


Performance of our Research Team


Quality and Integrated Management Systems

26


• CiVentiChem India has successfully obtained the following

certifications

• Currently follow Integrated Management Systems

• ISO-9001-2008 certification for Quality Management

Systems

• ISO-14001-2004 certification for Environmental

Management Systems

• ISO-18001-2007 certification for Occupational, Health and

Safety Management Systems (OSHA)

27

ISO Certifications


Chemistry Experience - Case Studies

28


Route Scouting and Discovery Support Erlotinib Analogue

O

O

O

O N

N

HN

Erlotinib

Nitration

Reduction

Reduction

1 2 34

56

7

89

10

11 12

HO

HO

HO

HO

HO

OPh

O

OPh

O

O

OPh

O

NO2

O

HO

O

NO2

O

O

O

NO2O

O

O

O

NH2O

O

O

O

O N

N

OHO

O

O

O N

N

OH

H2N

EtOH

H2SO4O Br

O OTs

O

O

O

O N

N

Cl

H2N O

O

O

O N

N

HN

H2N

NNCO2Et

CO2Et CO2Et CO2Et

CO2EtCO2EtCO2Et

CO2H

N

N

NN N

Client wanted a compound with a reactive functional groupRe-designed the synthesis and delivered the product


Med Chem Support/Route Scouting

C-imatinib analogue

N

O

N

O

N

N

NHN

4

2

6

N

N

N

NH2

Br

CO2H CO2H

Br

CO2H

N

N

NHN

7

N

N

NHN

18

1

3

5

14 15 16

O2N NO2

N

NO2 NH2

O

N

N

N

HN

N

NNH2

CO2H

N

NN

17

O

O

O O

N

N

NHN

O

N

N

NH2

HN

19

N

N

NHN

O

N

NHN

Imatinib

Client wanted analog with a reactive functional groupRe-designed the synthesis with a new route and delivered the product with NH2 and maleimido groups


Med Chem Support-Focus Libraries

N

N

N

Ar OR1

R

Ar =

NH

O

Het

Het= Pyrazoles, Isoxazoles, Oxazoles, Piperidines, Piperazines, benzofurans & etc

OR1 = Alkyl, cyclopropyl, cyclobutyl & etc

R = Alkyls & Aryls

3-Alkyl/Aryloxy-4-Alkyl/Aryl-5-Aryl/Heteroaryl-4H-1,2,4-triazoles



Ar =

Het= Pyrazoles, Isoxazoles, Oxazoles, Piperidines, Piperazines, benzofurans & etc

NO

NH2

Ar

Aryl/Hetero aryl

O

4-(1-Aryl/Heteroaryl-1,2,3,6-tetrahydropyridin-4-yl)benzamides

NN

NO2

NH

O

R1

R

R = Alkyl & ArylR1 = Substituted Aryls, heteroaryls,

cycloproppys and Pieridinyls

1-Alkyl/Aryl-4-nitro-N-Aryl/Heteroaryl-1H-pyrazole-3-carboxamide



N

S

N

N

X

HNR

5-Halo-N-Aryl/heteroaryl/alkylimidazo[2,1-b][1,3,4]thiadiazol-2-amines

R = Alkyl/Aryl/Hetero aryls & etcX = Br & I

N

N

N

OO

R

O

R = Alkyls, Aryls & Hetero aryls

ethyl 2-(4/5-(Alkyl/Aryloxymethyl)-1H-1,2,3-triazol-1-yl)acetates


Reference Standards for Med Chem Support

S

O

HN

NClHN

N

NMe

NN

HO

Dasatinib

O

O

O

O N

N

HN

ErlotinibN

N

NHN

HN O

N

N

Imatinib

N

N

Cl

O

NH

F

O

HN

SOMe

O

LapatinibHN

OEt N

CN

O

Cl

N

O

NNiratinib

N

N

NHN

O NH

N CF3N

NilotinibNH

NN

N

N

N

Pazopanib

SO2NH2

HNNH

ON

NH

F

OSunitinib


Reference Standards for Med Chem Support

N N

HN

N N

OH

OO

GSK-3B-XI

HN

O OHO

F

F

O

O

O

Firatigrast/SB-683699/T-0047

N

HN

O OHO

F

F

N

O

O AJM - 300

HNNH

ON

NH

F

OSunitinib Analogue

NH

MeN N

O

O

O

Trequinsin

N

O

S

NHO

O

Pioglitazone

N

N

N

F Br

O

O

N

Vandetanib


New Route & Process Development

Hexahydrofuro[2,3-b]furan-3-ol moiety

O

O

OHHexahydrofuro[2,3-b]furan-3-ol

(Bisfuran Alcohol)

NHHO

O

N

O

O

O

SO

O

Brecanavir(GW640385)

OO

N

S

O

NHHO

O

N

O

O

O

H2N

S

OO

Darunavir(TMC-114)

HN

HO

O

N

O

O

O

H2N

SO

O

GS-9005

HNP

O

O

O

OO

NCE

Bis-THF alcohol -A Key intermediate in many antiviral drugsOur goal: Develop a new route for use in Med ChemThen develop a process for manufacturing


New Route & Process Development Hexahydrofuro[2,3-b]furan-3-ol moiety

CO2EtEtO2C

OH Br

LDA CO2Et

CO2Et

OHLAH

OH

HO

OH

HO

Acetone

PTSAO

O

O

MeO

Oxidation

CHO

OO

CSA

MeOH

O

MeO

O

O3 CSA

MeOH

O

O

HO

OH OH

Enantioselective Synthesis

Reported synthetic route

•Problems with enantiomeric purity•Scalability



O OH OO

O

O OO

O

New Route Development to make chiral alchol

Process Development O

OH O

I

O

1) Cobaloxime

NaBH4/NaOH

CH2Cl2 / 0°C

O

O

O

2) NaIO4K2OsO2 (OH)4

O

O

HO

NaBH4O

O

HO

Enzymatic

ResolutionAcetylation(2) (4) (5)(1) NIS

(3)

O

O

AcO

Synthesis and Optical Resolution

Initial Goal:•Make small quantity to make 100 gm of API•After this is delivered, client wanted to file for IND, hence needed 10 Kg•No luxury of time as it was needed urgently•Brute forced the synthesis and delivered the product•Two enantiomers were separated by column chromatography



Process Development – Objectives•Eliminate hazardous radical reactions•Avoid column purification of resolution mixture•Improve economics of API route- 12 step synthesis

Avoided column chromatography by developing a solid derivative that can be separated by filtration from resolution mixture

Preparation Bis THF Active Fragment

O

O

HO

O O

O

O

O N

O

O

NO O

O

N

O

O O

O

•Redesigned API route where this expensive chiral piece comes at penultimate step•In earlier synthesis it was used in second step-Thus improving economies by several fold•Made 500 gm of API with the route which is being used now


New Route & Process Developmentfor a key intermediate for API

potent farnesyl protein transferase (FPT) inhibitor

Inhibition of CholesterolSynthesis by Inhibiting

Squalene Synthase

BocNCO2H

O

O

N

Cl

OH

ON

O

O CO2Et

Br Br

Cl

N

O

NH

Piperidine-4-acetic acid is a key intermediate


New Route & Process Development Piperidine-4-acetic acid is a key intermediate

Lonarfanib

Br Br

Cl

N

O

NH

N

O N N

OO

N

OH

NH

OH

CO2Et CO2H

CO2Et

CO2Et

CO2Et

N

O

NO

O

OMs


Process Development 4-(4-Chloro-pyrimidin-2-ylamino)-

benzonitrile for Anti Viral drugs

N

N

NH

N

Cl

NH

N

N

NH

N

Depivirin (TMC 120)

NH

N

N

N

NH

N

Rilpivirine (TMC 278)

O

N

NN

HN N

NH2Br

Etravirine (TMC 125)


Process Development Synthesis of di-tert-butyl chloromethyl phosphateSynthesis of di-tert-butyl chloromethyl phosphate

for The Synthesis of ProdrugsProdrugs

OP

O

O

O Cl

HO P

O

OH

O N

N

F

FF

O

OCinnarizine prodrugantihistamine

O

NN

N

Cl

Loxapine prodrug

OHP

O

HO

O

F

FF

O

O

antipsychotic

N

S

N

NN

N

O

F

F

Ravuconazole (BMS-207147) Prodrug

OP

O

O

O

2Na

antifungal

NO

I

I

O

O

HOP

O

OH

O

F

FF

O

O Amiodarone Prodrug

antiarrhythmic agent

2NaN

NS NH

OO

OP

O OH

O

Water Soluble Prodrugs of Anthelmintic Benzimidazole

N

O

F

F

NH

O

S

N

HOPO

OH

O

Lu AA47070 ProdrugSelective hA2A Receptor Antagonist


Innovative Chemistry- (+) Lactacystine

NH

O

OHOOHO

NH2

O

16 Steps

OHN

O

O

S

HN

O

OH

O

HO H

Isolated in 1991 by Omura et. Al from Steptomyces sp.

First non-protein neurotropic factor

Highly useful pharmacological tool

Lactone is key active component and acts by acylation of threonine residue


Innovative ChemistryOrganic synthesis in Aqueous mediumWater as a solvent:Water as a solvent:

3,4-dihydro-2H-benzo[b]thiazine-3-ones 3,4-dihydro-2H-benzo[b]thiazine-3-ones 1,2,3,4-tetrahydro-2-quinoxalinones1,2,3,4-tetrahydro-2-quinoxalinones 2,6-dialkyl-3,5-dicarboxyl-1,4-dihydropyridines & others

NH

HN

O

R

1,2,3,4-tetrahydro-2-quinoxalinones

NH

S

O

R

3,4-dihydro-2H-benzo[b]thiazine-3-ones

NH

O

O

O

O

R

2,6-dialkyl-3,5-dicarboxyl-1,4-dihydropyridines

N

X N

R1

R2

R


Summary of Chemistry Expertise

Medicinal Chemistry Support

New Route Development

Process Optimization

Innovative Chemistry

Reference Standards for Med Chem

Support


Chemistry Experience Proprietary Building Blocks Developed at CiVentiChem

47


Key building blocks for NCE’s 7-Azaindoles

Selective B-Raf inhibitors

Selective, ATP-competitive inhibitors of the mTOR

Selective Inhibitor of Aurora B/C Kinase

Active potent VEGFR-2 inhibitor

N N

NO

N O

OHN

HN

O N

N NH

RR1

R=4-Cl, Br, F, CN, OMe; 5-Cl, Br, F, I, CN, CHO, CO2Me 6-Cl, OHR1=3-Cl, Br, I, CN, CHO, CO2Me

N NH

NN HN

HN

OF

F

F

N NH

NN HN

HN

O

N

NNH

NH

NN

N N N

O


Key building blocks for NCE’s 1H-Indazoles

Potent and Selective Inhibitors of Factor Xa

Potent TRPV1 Antagonist for

Pain Management (ABT-102)

Novel 5-HT6 Receptor Antagonists

Potent CDC7 inhibitors

N

NH

N

F

N

N

Me

O N

NH2

O

N

NH

NHN

Cl

O

N

N

S OO

N

H2N

N

HN

NHHN

O


Azaindoles & (1H)-Indazoles

N NH

X = I

X

N NH

X

N NH

4,5,6,7-Azaindoles and Mono/DiSubstituted 7-Azaindole:

X = Cl, Br, I, CN & CHO

X = Cl, Br & OH

NH

N

4,5,6Azaindoles

N NH

YX

X

N NH

XY

X=Cl, Y=Cl, Br, I, CN. CHOX=Br, Y=Cl, I, CN, CHO

X=Br, Y=Cl, Br, I, CN. CHO

Substituted IH-Indazoles:

X=Br, CHO, CO2Me, CO2H, CH2NH2X = Br

NH

NNH

NNH

N

X X

X

NH

N

X

X= H, Cl, I, Br, CN & CO2H

NH

NX

Y

X=Br, CHO, CO2Me, Y=Cl, I


Drug Intermediates in Bulk

N NH

XCl

NH

N

X

N NH

CO2H

NH

NH2

HCl

NH

N

RO2C

R = H, Me

NH

N

R = H, Me

RO2C

NCl Cl

O

N NH

X

NH

N

Br

N NH

X

N NH

BrX

X = Cl, I

OH

Br

O O

SO

O

NH2N

HNNH2

Ph

X = Cl, Br, IX = H, Br, I X = Cl, Br, I

X = Cl, Br

NH

N

Br

N

N NH

OH


Pyrimidines

Aryl β-Keto & Diketo esters

O O

Y

O O

OEt

R=Cl, Br, F, I, Me, OMe, CF3, Y=OEt, CO2Et

R NH

O O

OEt

N

O O

OEt

O

O O

OEt

Aryl Beta Keto & Diketo Esters

R= Cl, Br, F, OMe, Me;

N

N

Cl

NH

RN

N

R

O

O

R1

N

N

R

O

O

R1

N

N

R

OO

R= Cl, Br, F, OMe, Me;R1=H, Me & Et

R= AlkylsR1=H, Me & Et


Pyrazole Derivatives

Isoxazole Derivatves

N NH

O

O

R1

X

N NH

O

O

R1

X R

N NH

R

O

O

R1N N

H

X OO

R1

N NH

X OO

R1

R N NH

RO

OR1

X= Cl, Br, F, OMe, Me; R=H & Me, Et, Pr, iPrR1=H, Me & Et

X= Cl, Br, F, OMe, Me; R=H & Me, Et, Pr, iPrR1=H, Me & Et

R=H & Me, Et, Pr, iPr, CyPrR1=H, Me & Et

ON

R

O

O

R1

R= Cl, Br, F, OMe, Me; R1=H, Me & Et

NO

R= Alkyls & Substituted Aryls R1=H, Me

NO

R

R= Cl, Br, F, OMe, Me; R1=H, Me

H2N

R1

R

O

O

R1


2-Naphthol Derivatives (R & S Isomers)

Reagents & Catalysts

OH

OH

OMOM

OMOMOTs

OTsOAc

OAcOH

OH

Br

Br

NH

OH

R

R

R

RR-DPP & S-DPPR & S IsomersR=H & CF3

NH

O

R

R

R

RR & S IsomersR=H & CF3

Si N

O

O

O O

O

N

O

O

DSC

N

Co

N

N

N

O O

H

O OH

Py

Cobaloxime

N N

N

HNNH

O

O


Facilities

55


Facilities - India

Hyderabad, India

• Four Synthetic Laboratories • 6 Fume hoods in each lab

• Analytical Capabilities (HPLC, GC, LC-MS)

• Provide Competitive Large-Scale Production

• Provide Chemists (FTEs)• Access to Modern Library & Exceptional

Scientific Talent from National Labs 56


Facilities - IndiaPlant - Equipment Configuration• Stainless Steel Reactors:

– 2000 L(1); 1600 L(2); 1000 L(1); – 500 L(2); 350 L(4) & 250 L (4)

• GL Reactors: – 2000 L(1); 1000 L(2); 630 L(1) &250 L(1)

• Autoclave (Hydrogenation) – 350 L(1) Yet to be installed and– 2.0 L(1) & 0.5 L(1)

• Auxiliary Filtration, Drying and Milling• Separate QC Laboratory and Documentation Center

57


Manufacturing EquipmentSS316 Reactor SS316 Reactor 1200L1200L 2 No's2 No'sSS316 Reactor SS316 Reactor 1000L 1000L 1 No1 NoGlass Lined Reactor Glass Lined Reactor 1000L1000L 1 No1 NoSS316 Reactor SS316 Reactor 250L250L 2 No's2 No'sSS316 Reactor SS316 Reactor 350L350L 2 No's2 No'sSS316 Reactor SS316 Reactor 2000L2000L 1 No1 NoSS316 Reactor SS316 Reactor 500L500L 1 No1 NoGlass Lined ReactorGlass Lined Reactor 160L160L 2 No's2 No'sGlass Lined ReactorGlass Lined Reactor 250L250L 1 No1 NoGlass Lined ReactorGlass Lined Reactor 500L500L 1 No1 NoGlass Lined ReactorGlass Lined Reactor 1600L1600L 1 No1 NoCentrifuze SS316 Centrifuze SS316 36“36“ 1 No1 NoCentrifuze SS316Centrifuze SS316 24" 24" 1 No1 NoCentrifuze SS316Centrifuze SS316 18" 18" 1 No1 NoRotocone GL dryerRotocone GL dryer 250 L250 L 1 No1 NoRotocone SS316 dryerRotocone SS316 dryer 50 L50 L 1 No1 NoTray dryerTray dryer 12 trays12 trays 1 No1 NoVacuum Tray dryerVacuum Tray dryer 6 Tray6 Tray 1 No1 NoTray dryerTray dryer 24Tray24Tray 1 No1 NoSifterSifter 24“24“ 1 No1 NoMulti millMulti mill 25 Kg/Hr25 Kg/Hr 1 No1 NoSifterSifter 12“12“ 2 No's2 No'sMulti millMulti mill 10 Kg/Hr10 Kg/Hr 2 No's2 No'sCooling towerCooling tower 70 TR70 TR 1 No1 NoCooling towerCooling tower 30 TR30 TR 1No1NoVacuum Pumps Vacuum Pumps 300M300M33/Hr/Hr 4 No‘s4 No‘s

R&D , Stores and QCR&D Labs:R&D Labs:Fume HoodsFume Hoods 27 No’s27 No’s Cooling Tower 30TRCooling Tower 30TR 2 No’s2 No’s Vacuum Pumps 120M3/Hr Vacuum Pumps 120M3/Hr 4 No’s4 No’s Analytical Equipment:Analytical Equipment: HPLC (Quartanery & Gradient) HPLC (Quartanery & Gradient) 2 Nos 2 Nos Preparative HPLC, LCMS & GC - Preparative HPLC, LCMS & GC - 1 No Each1 No Each

Production Block

Utility Block Diesel Generator 180 KVA Diesel Generator 180 KVA 1 No1 NoOil Fired Boiler 1 Ton/Hr Oil Fired Boiler 1 Ton/Hr 1 No1 NoNN22 Generator 99.5 %, 5 m Generator 99.5 %, 5 m33/h/h 1 No1 NoDM Plant (with RO) 40 DM Plant (with RO) 40 mm33/Reg/Reg 1 No1 NoAir Compressor 70 CFM Air Compressor 70 CFM 1 No1 No

Corrosive Block FRP Reactor 2000L FRP Reactor 2000L 1 No1 No Glass Lined Reactor 1600 L Glass Lined Reactor 1600 L 1 No1 NoGlass Lined Reactor 630L Glass Lined Reactor 630L 1 No1 NoGlass Lined Reactor 100L Glass Lined Reactor 100L 1 No1 NoHydrogenator -SS316 -350L (25 Kg) Hydrogenator -SS316 -350L (25 Kg) 1 No1 NoBrine Compressor (-20 DEG) 15 TR Brine Compressor (-20 DEG) 15 TR 1 No1 NoCooling tower 165 TR Cooling tower 165 TR 1 No1 NoCentrifuze SS316 & halar coat 36“ Centrifuze SS316 & halar coat 36“ 1 No1 No


Analytical Facilities CiVentiChem, IndiaS. No. Name of the Instrument No. of instruments Make

1 HPLC With PDA detector 2 Agilent2 HPLC With VWD detector 1 Agilent3 HPLC with PDA Detector 1 Agilent4 Preparative HPLC 1 Agilent5 GC with FID Detector 2 Agilent6 LCMS 2 Agilent & Schimadzu7 Analytical Balance 2 Denver, Sartorius8 Ultrasonicator 2 PCi9 Digital PH-Meter 2 POLOMON & GLOBAL

10 Microprocessor PH-Meter 1 GLOBAL11 Conductivity & TDS Meter 1 GLOBAL12 Melting Range Apparatus 2 POLOMON13 Karl Fischer Apparatus 2 POLOMON14 Milli-Q Water purification

system2 Millipore


For inquiries, please contact:

Dr. Venugopal Rao VeeramaneniCiVentiChem India Limited[Formerly known as Indus BioSciences (P) Ltd.,]Plot No. 72/A, Part 2, Phase-I, I.D.A., Jeedimetla,Hyderabad, A.P. , India..

Tel : +91-40-23197766/67/68 Ext: 228; Fax : +91-40-23091692Mobile: +91-9030026010; e-mail : [email protected] www.civentichem.com

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