Routes to Essential Medicines A Workbook for Organic Synthesis

This comprehensive workbook helps readers become familiar with the structures and synthetic challenges associated with nearly 300 essential medicines and gain the skills needed for pharmaceutical development.

• Highlights nearly three hundred medicines on the latest World Health Organization (WHO) Model List of Essential Medicines and their manufacturing routes
• Features exercises that equip students with the skills necessary to solve similar real-world problems
• Includes a retrosynthetic analysis for each commodity chemical and supplies an extensive list of key journal and information sites and a library of reagents, solvents, and conditions for many common organic reactions

Peter J. Harrington, PhD, is the owner and primary consultant for Better Pharma Processes LLC, Boulder, Colorado, USA. Dr. Harrington is a pharmaceutical process design and development expert with more than twenty years’ experience in timely process innovation for major pharmaceuticals. His publications include a book on pharmaceutical process chemistry for synthesis and several articles on organic and medicinal chemistry.

Introduction xix

A 1

Abacavir 1

Acetazolamide 3

Acetylcysteine 4

Acetylsalicylic Acid 4

Acyclovir 5

Albendazole 6

Allopurinol 7

Amidotriazoate 8

Amikacin 9

Amiloride 11

4-Aminosalicylic Acid 12

Amiodarone 13

Amitriptyline 15

Amlodipine 16

Amodiaquine 17

Amoxicillin 18

Ampicillin 20

Anastrozole 21

Artemether 23

Artesunate 24

Ascorbic Acid 26

Atazanavir 27

Atracurium Besylate 29

Atropine 32

Azathioprine 34

Azithromycin 35

Aztreonam 37

B 40

Beclomethasone Dipropionate 40

Bedaquiline 45

Bendamustine 47

Benznidazole 49

Benzoyl Peroxide 50

Benzyl Benzoate 51

Betamethasone 52

Bicalutamide 56

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viii Contents

Biperiden 57

Bisoprolol 58

Budesonide 59

Bupivacaine 62

C 63

Caffeine 63

Calcium Folinate/Folinic Acid 64

Capecitabine 65

Carbamazepine 67

Cefalexin 68

Cefazolin 69

Cefepime 71

Cefixime 73

Cefotaxime 75

Ceftaroline 77

Ceftazidime 81

Ceftriaxone 84

Chlorambucil 86

Chloramphenicol 87

Chlorhexidine 89

Chloroquine 90

Chloroxylenol 91

Chlorpromazine 92

Ciprofloxacin 93

Cisplatin, Carboplatin, Oxaliplatin 94

Clarithromycin 97

Clindamycin 99

Clofazimine 100

Clomifene 101

Clomipramine 102

Clopidogrel 103

Cloxacillin 105

Clotrimazole 106

Clozapine 107

Codeine 108

Colecalciferol 109

Cyclizine 112

Cyclophosphamide 113

Cycloserine 114

Cytarabine 114

D 116

Dacarbazine 116

Daclatasvir 117

Dapsone 119

Darunavir 120

Dasabuvir 122

Dasatinib 124

Delamanid 126

Desmopressin 129

Dexamethasone 131

Diazepam 136

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Contents ix

Diethylcarbamazine 137

Dihydroartemisinin 139

Diloxanide Furoate 140

Dimercaprol 141

Docetaxel 141

Docusate Sodium 145

Dolutegravir 145

Dopamine 147

Doxycycline 148

E 150

Efavirenz 150

Eflornithine 152

Emtricitabine 153

Enalapril 155

Entecavir 158

Ephedrine 160

Epinephrine 160

Ergocalciferol 162

Ergometrine 163

Estradiol Cypionate 164

Ethambutol 166

Ethinylestradiol 166

Ethionamide 167

Ethosuximide 169

Etonogestrel 169

Etoposide 173

F 175

Fentanyl 175

Fluconazole 176

Flucytosine 177

Fludarabine Phosphate 177

Fludrocortisone Acetate 179

Fluorouracil 180

Fluoxetine 181

Fluphenazine 182

Folic Acid 184

Fomepizole 185

Formoterol 186

Fosfomycin 189

Furosemide 191

G 192

Gemcitabine 192

Gliclazide 194

Glutaral 195

Glyceryl Trinitrate 196

H 197

Haloperidol 197

Halothane 199

Hydralazine 199

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x Contents

Hydrochlorothiazide 200

Hydrocortisone 200

Hydroxycarbamide 203

Hydroxychloroquine 204

Hyoscine Butylbromide 205

I 207

Ibuprofen 207

Ifosfamide 208

Imatinib 209

Iohexol 210

Ipratropium Bromide 212

Irinotecan 214

Isoflurane 217

Isoniazid 218

Isosorbide Dinitrate 219

Itraconazole 219

Ivermectin 223

K 226

Ketamine 226

L 227

Lactulose 227

Lamivudine 228

Lamotrigine 229

Latanoprost 230

Ledipasvir 235

Leuprorelin 239

Levamisole 241

Levofloxacin 242

Levonorgestrel 244

Levothyroxine 247

Lidocaine 248

Linezolid 249

Loperamide 251

Lopinavir 252

Loratidine 255

Lorazepam 257

Losartan Potassium 259

Lumefantrine 261

M 263

Mannitol 263

Mebendazole 264

Medroxyprogesterone Acetate 265

Mefloquine 269

Meglumine Iotroxate 270

Melarsoprol 271

Mercaptopurine 272

Meropenem 274

Mesna 278

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Contents xi

Metformin 279

Methadone 279

Methotrexate 280

Methyldopa 282

Methylprednisolone 283

Methylthioninium Chloride 288

Metoclopramide 289

Metronidazole 290

Miconazole 291

Midazolam 292

Mifepristone 295

Miltefosine 298

Misoprostol 299

Moxifloxacin 302

N 305

Naloxone 305

Neostigmine Methylsulfate 306

Nevirapine 307

Niclosamide 309

Nicotinamide 309

Nifedipine 310

Nifurtimox 310

Nilotinib 311

Nitrofurantoin 313

Norethisterone and Norethisterone Enanate 314

O 317

Ofloxacin 317

Ombitasvir 319

Omeprazole 320

Ondansetron 322

Oseltamivir 323

Oxamniquine 325

Oxytocin 327

P 330

Paclitaxel 330

Paracetamol 333

Paritaprevir 334

Penicillamine 339

Pentamidine 340

Permethrin 341

Phenobarbital 342

Phenytoin 343

Piperacillin 344

Piperaquine 346

Praziquantel 347

Prednisolone 349

Primaquine 350

Procarbazine 352

Progesterone 353

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xii Contents

Proguanil 356

Propofol 356

Propranolol 357

Propylthiouracil 358

Prostaglandin E1 359

Prostaglandin E2 362

Pyrantel 366

Pyrazinamide 367

Pyridoxine 367

Pyridostigmine Bromide 369

Pyrimethamine 369

Pyronaridine 370

R 373

Raltegravir 373

Ranitidine 376

Retinoic Acid (All-trans) 377

Retinol (Vitamin A1) 378

Ribavirin 380

Rifabutin 382

Rifampicin 384

Rifapentine 386

Risperidone 389

Ritonavir 390

S 395

Salbutamol 395

Simeprevir 397

Simvastatin 402

Sodium Calcium Edetate 404

Sofosbuvir 405

Spironolactone 408

Succimer 410

Sulfadiazine and Silver Sulfadiazine 411

Sulfadoxine 412

Sulfamethoxazole 413

Sulfasalazine 415

Suramin 416

Suxamethonium Chloride 418

T 419

Tamoxifen 419

Tazobactam 421

Tenofovir Disoproxil 423

Terbinafine 424

Testosterone 425

Tetracaine 427

Tetracycline 428

Thiamine 428

Tigecycline 430

Timolol 434

Tranexamic Acid 435

Triclabendazole 436

Trimethoprim 437

Tropicamide 438

U 440

Ulipristal Acetate 440

V 445

Valganciclovir 445

Valproic Acid 447

Vecuronium Bromide 448

Velpatasvir 452

Verapamil 459

Vincristine 460

Vinorelbine 461

Voriconazole 463

W 466

Warfarin 466

X 467

Xylometazoline 467

Z 469

Zidovudine 469

Zoledronic Acid 471

A Demonstration: Amiodarone 472

Appendix A 478

Appendix B 594

Appendix C 595

Index 000

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