Advanced Organic Chemistry - I

1. Ajay Kumar, M. Pharm. (Pharmaceutical Chemistry), NIET, Pharmacy Institute, Greater Noida, U. P., India. Advanced Organic Chemistry - I Unit – IV (B)

2. Ketoconazole Synthesis:- Cl C CH2Br Cl O 2-Bromo-1-(2,4-dichloro-phenyl)- ethanone + CH2OH CH CH2 OH OH Propane-1,2,3-triol Cl C CH2Br Cl OO CH2OH [2-Bromomethyl-2-(2,4-dichloro-phenyl)- [1,3]dioxolan-4-yl]-methanol C Cl O N N H Cl C CH2 Cl O O CH2COO N N [2-(2,4-Dichloro-phenyl)-2-imidazol-1-ylmethyl- [1,3]dioxolan-4-yl]-acetic acid phenyl ester CH3SO3Cl Cl C CH2 Cl O O H2C N N O SO2CH3 Methanesulfonic acid 2-(2,4-dichloro-phenyl)-2- imidazol-1-ylmethyl-[1,3]dioxolan-4-ylmethyl ester N N C CH3OH O Cl Cl C C N N OO CH2O NH N C CH3 O KETOCONAZOLE

3. H2N H2 C H2 C NH2 Ethane-1,2-diamine + CH3CN Acetonitrile Zn N N H CH3 2-Methyl-1H-imidazole P2O5, HNO3 N N H CH3 O2N 2-Methyl-5-nitro-1H- imidazole ClCH2CH2OH Reflux N N CH3 O2N CH2CH2OH 2-(2-Methyl-5-nitro-imidazol-1-yl)-ethanol / METRONIDAZOLE Metronidazole Synthesis:-

4. Miconazole Synthesis:- Cl Cl Br O + 2-Bromo-1-(2,4-dichloro-phenyl)- ethanone H N N 1H-Imidazole Cl Cl N O N 1-(2,4-Dichloro-phenyl)-2-imidazol-1-yl-ethanone NaBH4 Cl Cl N OH N 1-(2,4-Dichloro-phenyl)-2-imidazol-1-yl-ethanol Cl Br Cl Cl Cl N N Cl Cl 1-[2,4-Bis-(2,4-dichloro-phenyl)-butyl]-1H- imidazole / MICONAZOLE

5. N N O F F F 2,2,2-Trifluoro-1-imidazol- 1-yl-ethanone + O Acetophenone NaN(TMS)2 O O H CF3 4,4,4-Trifluoro-3-hydroxy-1-p-tolyl-but- 2-en-1-one S NH2 O O H N NH2 EtOH reflux S NH2 O O N N CF3 4-(5-p-Tolyl-3-trifluoromethyl-pyrazol-1-yl)-benzenesulfonamide / CELECOXIB Celecoxib Synthesis:-

6. PhNHNH2 + EtO O Me O 3-Oxo-butyric acid ethyl ester N N Ph O Me Met N N Ph O Me Me NaNO2/ H+ N N Ph O Me Me NO [H] N N Ph O Me Me NH2 PhCHO N N Ph O Me Me N Ph 5-Methyl-2-phenyl-2,4-dihydro-pyrazol-3-one 1,5-Dimethyl-4-nitroso-2- phenyl-1,2-dihydro- pyrazol-3-one 4-(Benzylidene-amino)-1,5-dimethyl-2-phenyl- 1,2-dihydro-pyrazol-3-one N N Ph O Me Me N Ph Me2SO4 Me H2O Benzylidene-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro- 1H-pyrazol-4-yl)-methyl-ammonium N N Ph O Me Me NH Me 1,5-Dimethyl-4-methylamino-2-phenyl-1,2-dihydro- pyrazol-3-one NaHSO3/ H2CO N N Ph O Me Me N Me SO3Na METAMIZOLE SODIUM MeOSO2 Metamizole Sodium Synthesis:-

7. Cl Cl C NH OO CH2OMs N N Methanesulfonic acid 2-(2,4-dichloro- phenyl)-2-[1,2,4]triazol-1-ylmethyl- [1,3]dioxolan-4-ylmethyl ester + NN CH3 CH3 OH 4-(4-Isopropyl-piperazin-1-yl)-phenol Cl Cl N N N O O O N N CH3 CH3 1-{4-[2-(2,4-Dichloro-phenyl)-2-[1,2,4]triazol-1-ylmethyl-[1,3]dioxolan-4-ylmethoxy]-phenyl}-4-isopropyl- piperazine / TERCONAZOLE Terconazole Synthesis:-

8. N Cl Cl 2,6-Dichloro-4-phenyl-quinoline NH2NH2 N Cl NH NH2 (6-Chloro-4-phenyl-quinolin-2-yl)-hydrazine CH3C(OC2H5)3 N Cl N N H3C 7-Chloro-1-methyl-5-phenyl-[1,2,4]triazolo[4,3- a]quinoline NaIO4/ RuO2 O N Cl N N H3C [5-Chloro-2-(3-methyl-[1,2,4]triazol-4-yl)- phenyl]-phenyl-methanone HCHO/ PBr3 O N Cl N N H3C CH2Br [2-(3-Bromomethyl-5-methyl-[1,2,4]triazol- 4-yl)-5-chloro-phenyl]-phenyl-methanone NH3 N Cl N N NH3C 8-Chloro-1-methyl-6-phenyl-4H-2,3,5,10b- tetraaza-benzo[e]azulene / ALPRAZOLAM Alprazolam Synthesis:-

9. NH NH2N H2N NH2 NH 1,2-Dihydro-pyrimidine- 2,4,5,6-tetraamine N H NH2N H2N NH2 NH2 1,2-Dihydro-pyrimidine- 2,4,5,6-tetraamine + Benzaldehyde C-5 Condensation CH N N NH2N NH2 HCN C H N H N NH2N NH2 CN NH2 alpha amino nitrile derivative OH Cyclisation N N N NH2N H NH2 NH2 H Dihydropyrazine derivative Spontaneous air-oxidation N N N NNH2 NH2 NH2 TRIAMTRENE Triamtrene Synthesis:-

10. Me O OEt O + H2N NH2 NH HN N O H2N Me 3-Oxo-butyric acid ethyl ester Guanidine 2-Amino-6-methyl-3H-pyrimidin-4-one POCl3 HN N Cl H2N Me 6-Chloro-4-methyl-1,6- dihydro-pyrimidin-2- ylamine H2/ Pd-C N NH2N Me 4-Methyl-pyrimidin-2-ylamine NHAc SO2Cl OH H2N S N H N N Me O O 4-Amino-N-(4-methyl-pyrimidin-2-yl)-benzenesulfonamide / SULFAMERAZINE Sulfamerazine Synthesis:-

11. H3CO H3CO H3CO H2 C H2 C COOC2H5 3-(3,4,5-Trimethoxy-phenyl)-propionic acid ethyl ester + HCOOC2H5 Na H3CO H3CO H3CO CH2 Formic acid ethyl ester COOC2H5 CH OH NH H2N NH2 H3CO H3CO H3CO CH2 N N H2N OH 3-Hydroxy-2-(3,4,5-trimethoxy-benzyl)-acrylic acid ethyl ester 4-Amino-5-(3,4,5-trimethoxy-benzyl)-pyrimidin-2-ol POCl3 NH3 H3CO H3CO H3CO CH2 N N H2N NH2 5-(3,4,5-Trimethoxy-benzyl)-pyrimidine-2,4-diamine / TRIMETHOPRIM Trimethoprim Synthesis:-

12. H3C C H2 C H2 C H2 C Cl O 6-Chloro-hexan-2-one + H N C2H5 H2C H2 C OH 2-Ethylamino-ethanol CH3 C H2 C H2 C CH2 O N C2H5 H2C H2 C OH 5-[Ethyl-(2-hydroxy-ethyl)-amino]-pentan-2-one H2, NH3 / [Raney-Ni] NH2 C H2 C H2 C CH2 O N C2H5 H2C H2 C OH 4-[Ethyl-(2-hydroxy-ethyl)-amino]-butyramide N Cl Cl N HN Cl C H2 C H2 C CH2 O N C2H5 H2C H2 C OH N-(7-Chloro-quinolin-4-yl)-4-[ethyl-(2-hydroxy-ethyl)-amino]-butyramide / HYDROXYCHLOROQUINE Hydroxychloroquine Synthesis:-

13. OH O H 3-Hydroxy-benzaldehyde OEtOEt NH2 OH N OEt OEt N OH Isoquinolin-7-ol N OH N 8-Piperidin-1-ylmethyl-isoquinolin-7-ol N OH CH3 N H OH CH3 8-Methyl-1,2,3,4-tetrahydro- isoquinolin-7-ol8-Methyl-isoquinolin-7-ol Quinine Synthesis:-

14. NCl Cl 4,7-Dichloro quinoline + HNH H C (CH2)3N(C2H5)2 CH3 4-Amino-1-diethylamino pentane Condensed NCl HN CH (CH2)3N(C2H5)2 CH3 CHLOROQUINE Chloroquine Synthesis:-

15. Cl Cl CO2H 2,4-Dichloro-benzoic acid + NH2 OMe 4-Methoxy-phenylamine Cu/ K2CO3 CO2H H NCl OMe 4-Chloro-2-(4-methoxy-phenylamino)-benzoic acid POCl3 NCl Cl OMe 6,9-Dichloro-2-methoxy-acridine H2N (CH2)3 Me N Et Et NCl HN OMe (CH2)3 NEt2 QUINACRINE Quinacrine Synthesis:-

16. NO2 OMe NH2 3-Methoxy-4-nitro- phenylamine MeSO2Cl NO2 OMe N H S CH3 O O N-(3-Methoxy-4-nitro-phenyl)-methanesulfonamide Fe/ HCl H2N OMe N H SO2Me N-(4-Amino-3-methoxy-phenyl)- methanesulfonamide N Cl N HN MeO H N SO2Me AMSACRINE Amsacrine Synthesis:-

17. N H S Cl 2-Chloro-10H-phenothiazine + Cl N N Me 1-(3-Chloro-propyl)-4-methyl-piperazine NaNH2 N S Cl N N Me 2-Chloro-10-[3-(4-methyl-piperazin-1-yl)-propyl]-10H-phenothiazine / PROCHLORPERAZINE Prochlorperazine Synthesis:-

18. N H S 10H-Phenothiazine + Cl N (3-Chloro-propyl)-dimethyl-amine NaNH2 N S N Dimethyl-(3-phenothiazin-10-yl-propyl)- amine / PROMAZINE Promazine Synthesis:-

19. S N H Cl 2-Chloro-10H-phenothiazine + Cl H2 C H2 C H2 C N CH3 CH3 (3-Chloro-propyl)-dimethyl-amine Reflux in presence of toluene and sodamide S N Cl H2C H2 C H2 C N CH3 CH3 [3-(2-Chloro-phenothiazin-10-yl)-propyl]-dimethyl-amine / CHLORPROMAZINE Chlorpromazine Synthesis:-

20. NHMe NHMe O 1,3-Diimino-propan- 2-one + EtO CN O Cyano-acetic acid ethyl ester Ac2O MeN CN O NHMeO 1-(2-Cyano-acetyl)-1,3-dimethyl-urea NaOH N N O NH2O 6-Amino-1,3-dimethyl- 1H-pyrimidine-2,4-dione HNO2 N N O NH2O NO 6-Amino-1,3-dimethyl-5- nitroso-1H-pyrimidine-2,4-dione [H] N N O NH2O NH2 5,6-Diamino-1,3-dimethyl- 1H-pyrimidine-2,4-dione HCONH2 N N O O N H N 1,3-Dimethyl-3,7-dihydro-purine-2,6-dione / THEOPHYLLINE Theophylline Synthesis:-

21. NH2 C NH2 O Urea + OC2H5 O C2H5O O Malonic acid diethyl ester N N O O O H H Pyrimidine-2,4,6-trione HNO2 N N O O O H H NO 5-Nitroso-pyrimidine- 2,4,6-trione Sn/ HCl N N O O O H H NH2 5-Amino-pyrimidine- 2,4,6-trione H-N=C=O N N O O O H H H N C NH2 O (2,4,6-Trioxo-hexahydro-pyrimidin-5-yl)- urea N N O O H H N N H H O Tetrahydro-purine-2,6,8-trione PCl5 N N Cl Cl N N H Cl 2,6,8-Trichloro-9H-purine NaOH N N OH Cl N N H Cl 2,8-Dichloro-9H-purin-6-ol HI N N OH N N H 9H-Purin-6-ol P2S5 N N SH N N H 9H-Purine-6-thiol / MERCAPTOPURINE Mercaptopurine Synthesis:-

22. N N N N Cl Cl OH NH3 N N N N Cl H2N OH HI N N N N H2N OH P2S5 N N N N H2N SH THIOGUANINE Thioguanine Synthesis:-

Advanced Organic Chemistry - I

Advanced Organic Chemistry - I

Recomendados

Más contenido relacionado

La actualidad más candente

La actualidad más candente(20)

Similar a Advanced Organic Chemistry - I

Similar a Advanced Organic Chemistry - I(19)

Más de Ajay Kumar

Más de Ajay Kumar(8)

Último

Último(20)

Advanced Organic Chemistry - I