Synthesis Of Hetero-cyclic Drugs 2

synthesis of hetero-cyclic drugs which act as anti-malarial drugs where you get all information about synthesis, preparation, properties, uses of drugs.

1. Synthesis of heterocyclic drugs Prepared by : Panchal Roshni Rameshbhai M.Pharm 1 st sem (pharmaceutical chemistry) Parul institute of pharmacy 1

2. Contents: Introduction Quinine Chloroquine Hydroxychloroquine Quinocrine Amsacrine 2

3. Introduction: A Heterocyclic compound are those which has atoms of at least two different elements of its ring. Heterocyclic chemistry is a branch of organic chemistry dealing with the synthesis, properties and applications of these heterocycles . 3

4. Quinine 4

5. Properties: Molecular formula : C 20 H 24 O 2 N 2 Molecular weight : 324.4 g/mol Chemical name : chinin , quinine, qualaquin Solubility : soluble in water and alcohol Color : white crystalline powder State : solid Source : cinchona bark Melting point : 177 ̊ C 5

6. Method of preparation: Synthesis starts from m- Hydroxybenzaldehyde (2) obtained from benzaldehyde (1) by nitration, where reduction of nitro group with stannous chloride, diazotisation and treatment with boiling water. Then compound (2) reacts under 2,2-diethoxyethanamine and sulfuric acid to form compound (3) which further under goes mannich reaction to form compound (4). Then compound (4) treated with sod. Methoxide at 220 ̊ C to form compound (5) which further under goes reduction to form compound (6) which in presences of acetic anhydride to form compound(7). Which further reacts with CrO3 and acetic acid to form compound(8) which further under goes separation to form compound(9) and (10) which under goes reduction to form compound(11) where oxime converted to amine. Now compound(11) under goes deacetylation to form alkene compound(12) which reacts with benzoyl chloride to form compound(13) Compound(13) treated with ethyl quininate (14) under claisen condensation to form compound(15) , in which addition of HCl to maintain acidity to form compound(16) , where further addition of sod. Hypobromite and sod. Hydroxide to form compound(17). And last compound(17) treated with Aluminium or ethanol or sod. Ethoxide to form Quinine. 6

7. Synthesis: 7

8. 8

9. 9

10. Uses: Malaria: Uncomplicated resistant falciparum malaria Complicated and severe malaria including cerebral malarial Treatment of leg cramps. 10

11. Chloroquine 11

12. Properties: Molecular formula : C 18 H 26 N 3 Cl Molecular weight : 319.9 g/mol Chemical name : aralen , nivaquin Solubility : soluble in water and methanol Color : white crystalline powder State : solid Melting Point : 87 ̊ C 12

13. Method of preparation: STEP:1 – Synthesis of 4,7-dichloroquinoline Take m- chloroaniline (1) with diethyl 2-oxosuccinate(2) was performed to form compound(3) Then cyclization of intermediate with NaOH / water and HCl to form compound(4) When treated with POCl3 in presence of heating CO2 removed to form 4,7-dichloroquinoline(7). STEP:2- Preparation of 1-diethyl amino-4-amino pentane Take ethylene oxide(8) with diethylamine (9) to give compound (10) Which treated with acetone to give compound (11) Further reduction of compound(6) by H2 /Ni and NH3 to give 1-diethyl amino-4-aminopentane(12). STEP:3- Condensation Condense the product of step-1 and step-2 to form chloroquine (13) . 13

14. Synthesis: Step:1 14

15. Step:2 15

16. Step:3 condensation of the product of step 1 and step 2 16

17. Uses: It is mainly used as anti-malarial. Act as antihistaminic and anti-inflammatory. It is used to treat hepatic amoebiasis, rheumatoid arthritis. 17

18. hydroxychloroquine 2-[4-[(7-chloroquinolin-4-yl)amino] pentyl-ethylamino ]ethanol 18

19. Properties: Molecular formula : C18H26N3ClO Molecular weight : 335.9 g/mol Chemical name : Oxichloroquine ,Oxychlorochin Solubility : soluble in water, insoluble in ethanol and ether Color : white crystalline powder State : solid Melting point : 90 ̊C 19

20. Method of preparation: STEP:1- Preparation of side chain Take 1-chloro pentane-4-one(1) and 2-( ethylamino )ethanol(2) with the removal of HCl to produce compound(3). Then reductive amination of compound(3) by NH3 / H2 to produce N-Ethyl-N-(2-hydroxyethyl)-4-amino pentylamine (4). STEP:2- Condensation Now 4,7-dichloro quinoline (5) and product of step-1(4) condensed with the removal of HCl to produce Hydroxychloroquine (6). 20

21. Synthesis: Step: 1 21

22. Step:2 22

23. Uses: It is less toxic then chloroquine and used in the place of chloroquine against normally sensitive strains. It is mainly used as an antimalarial It is also used for treatment of rheumatoid arthritis and lupus erythematoses. 23

24. quinacrine 6-chloro-N-(5-(diethylamino)pentan-2-yl)-2-methoxyacridin-9-amine 24

25. Properties: Molecular formula : C 23 H 30 N 3 ClO Molecular weight : 400 g/mol Solubility : soluble in water and ethanol insoluble in alcohol, benzene and chloroform Color : bright yellow powder State : solid Melting point : 248-250 ̊C 25

26. Method of preparation: Take 2,4-dichloro benzoic acid(1) and 4- methoxy aniline(2) with KOH to produce compound(3) Then cyclization of compound(3) in the presence of POCl3 to produce compound(4) Ketonation of compound (4) to form compound(5) when compound (5) is treated with POCl3 and group-R with the removal of HCl to form quinacrine (7). 26

27. Synthesis: 27

28. Uses: Acts as a schizontocidal Used in the treatment of leishmaniasis and some tape worm infections . 28

29. AMSACRINE 29

30. Properties: Molecular formula : C 21 H 19 N 3 O 3 S Molecular weight : 393.5 g/mol Solubility : soluble in chloroform, ethanol and methanol insoluble in water Color : yellow crystalline powder State : solid Melting point : 235 ̊C 30

31. Method of preparation: STEP:1- Synthesis of 9-chloro-acridine Take 2-chloro-benzoic acid(1) and aniline(2) to form compound (3). Which further reacts with POCl3 to give 9-chloro-acridine(4) STEP:2- Take 3-methoxy-4-nitroaniline(5) with methanesulfonyl chloride(6) to give compound (7) which further reacts with presence of Fe,HCl to form 4-aminomethanesulfony- m- anisidine (8). STEP:3- Condensation Now the product of step-1 and step-2 condensed together to form amsacrine (9) . 31

32. Synthesis: Step:1 32

33. Step:2 33

34. Step:3 34

35. Uses: Act as anti-cancer agents Used to treat acute adult leukemia. Also used to treat malignant lymphomas 35

36. THANK YOU 36