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2022-85-7

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2022-85-7 Usage

Overview

A fluorinated pyrimidine, 5-flucytosine (fluorocytosine; 5-FC, Fig. 1), was initially developed as a potential anti-cancer agent but it was not sufficiently effective in the field of cancer chemotherapy[1]. Later, 5-FC proved to be active in experimental candidiasis and cryptococcosis in mice[2] and was used to treat human infections[3]. In addition to its activity against Candida and Cryptococcus, 5-FC also has an inhibitory activity against fungi causing chromoblastomycosis[4]; however, it is ineffective against infections caused by filamentous fungi. 5-FC has a high prevalence of primary resistance in many fungal species. Due to this primary resistance, 5-FC is used mainly in combination with other antifungals (primarily amphotericin B, AmB) and more recently it has been investigated in combination with other agents including fluconazole (FLU), ketoconazole (KTZ), itraconazole (ITRA), voriconazole (VORI) and echinocandins (e.g., micafungin, MICA and caspofungin, CAS). It is used only rarely as a single agent. Flucytosine (5-FC) is a synthetic antimycotic compound, first synthesized in 1957. It has no intrinsic antifungal capacity, but after it has been taken up by susceptible fungal cells, it is converted into 5-fluorouracil (5-FU), which is further converted to metabolites that inhibit fungal RNA and DNA synthesis. Monotherapy with 5-FC is limited because of the frequent development of resistance. In combination with amphotericin B, 5-FC can be used to treat severe systemic mycoses, such as cryptococcosis, candidosis, chromoblastomycosis and aspergillosis. Figure 1 the chemical structure of Fluorocytosine ;

Mechanism of action and resistance

5-FC is most active against yeasts, including Candida, Torulopsis and Cryptococcus spp., and against the dematiaceous fungi causing chromomycosis (Phialophora and Cladosporium spp.) and Aspergillus spp.[5] The MICs of 5-FC vary from 0.1 to 0.25 mg/L for these fungal species. In Emmonsia crescens, Emmonsia parva, Madurella mycetomatis, Madurella grisea, Pyrenochaeta romeroi, Cephalosporium spp., Sporothrix schenckii and Blastomyces dermatitidis, MICs vary from 100 to 1000 mg/L.14 5-FC is also active against some protozoa, including Acanthamoeba culbertsoni both in vitro and in vivo and Leishmania spp. in patients.[5] Antimycotic activity of 5-FC results from its rapid conversion into 5-fluorouracil (5-FU) by the enzyme cytosine deaminase, within susceptible fungal cells. There are two mechanisms involved by which 5-fluorouracil exerts its antifungal activity. The first mechanism includes the conversion of 5-fluorouracil through 5-fluorouridine monophosphate (FUMP) and 5-fluorouridine diphosphate (FUDP) into 5-fluorouridine triphosphate (FUTP)[6]. FUTP is further incorporated into fungal RNA in place of uridylic acid; this alters the aminoacylation of tRNA, disturbs the amino acid pool and inhibits protein synthesis[6]. The second mechanism is the metabolism of 5-FU into 5-fluorodeoxyuridine monophosphate (FdUMP) by uridine monophosphate pyrophosphorylase[6]. FdUMP is a potent inhibitor of thymidylate synthase, which is a key enzyme involved in DNA synthesis and nuclear division[7]. Thus, 5-FC acts by interfering with pyrimidine metabolism and protein synthesis in the fungal cell. These activity results in cell lysis and death. The occurrence of resistance with the use of 5-FC has been widely described and precludes use of 5-FC as a single agent[8, 10] Two basic mechanisms of resistance can be distinguished: (i) certain mutations can result in a deficiency in the enzymes necessary for cellular transport and uptake of 5-FC or for its metabolism (i.e. cytosine permease, uridine monophosphate pyrophosphorylase or cytosine deaminase);[9,11] (ii) resistance may result from increased synthesis of pyrimidines, which compete with the fluorinated antimetabolites of 5-FC and thus diminish its antimycotic activity.[9] It has been shown that defective uridine monophosphate pyrophosphorylase is the most frequently occurring type of acquired 5-FC resistance in fungal cells.[12] Normark & Sch?nebeck have reported that two different phenotypes of 5-FC-resistant strains can be recognized:[10] strains of resistance phenotype class 1 are not affected by 5-FC at high concentrations (these are the totally (intrinsically) resistant strains), while those of class 2 are susceptible to 5-FC at low concentrations but, after long exposure to 5-FC (even at high concentrations) resistance develops (these are said to be partially resistant or to have acquired resistance). Development of resistance in the latter strains probably results from selection of non-susceptible mutants, leading to a secondary resistant population.[9] The incidence of resistance to 5-FC varies between species.20 Up to 7–8% of intrinsically resistant strains are found among pretreatment isolates of C. albicans, unspeciated candida and Torulopsis glabrata. In C. neoformans the incidence of resistance is lower (1–2%), but in Candida spp. other than C. albicans it is 22%, because of the prevalence of generally less sensitive species such as Candida tropicalis and Candida krusei[13]. The exact incidence of primary 5-FC resistance is not clear. Different investigators report rates ranging between 8% and 44% for Candida spp[14]. Possible factors contributing to this wide range include the susceptibility methods used, local factors involving use of antifungal agents and differences in the prevalence of various Candida spp[14].

Pharmacokinetic and dosage

5-FC is absorbed very rapidly and almost completely: 76–89% is bioavailable after oral administration.[16] In patients with normal renal function, peak concentrations are attained in serum and other body fluids within 1–2 h.[15, 16]. 5-FC penetrates well into most body sites, including cerebrospinal, vitreous and peritoneal fluids, and into inflamed joints, because it is small and highly water-soluble and is not bound by serum proteins to a great extent[15-17]. 5-FC is principally eliminated by the kidneys and the plasma clearance of the drug is closely related to creatinine clearance[15, 17]. 5-FC is only minimally metabolized in the liver. Renal elimination is via glomerular filtration; no tubular resorption or secretion takes place. The half-life of 5-FC is c.3–4 h in patients with normal renal function, but can be extended up to 85 h in patients with severe renal insufficiency.[12, 16, 18] Renal insufficiency alters 5-FC pharmacokinetics since it slows absorption, prolongs serum half-life and decreases clearance[15]. The apparent volume of distribution of 5-FC approaches that of total body water and is not altered by renal failure. Dosage must be adjusted in patients with renal impairment. Various recommendations have been made[15-18]. Daneshmend & Warnock have suggested the following guidelines for the administration of 5-FC to patients with renal insufficiency.[15]. In patients with a creatinine clearance of >40 mL/min, a standard dose of 37.5 mg/kg every 6 h should be used. If the creatinine clearance is between 20 and 40 mL/min, the recommended dose is 37.5 mg/kg every 12 h. In patients with a creatinine clearance of <20 mL/ minute, the dose of 5-FC should be 37.5 mg/kg once daily. Finally, if the creatinine clearance is <10 mL/min, frequent determinations of 5-FC concentration should be used as guidance for the frequency of dosing.

Toxicity and side effects

5-FC is known to have some relatively minor side effects, such as nausea, vomiting and diarrhoea, it also has more severe side effects, including hepatotoxicity and bonemarrow depression. Gastrointestinal side effects, the most common and least harmful side effects associated with 5-FC treatment, include nausea, diarrhoea and, occasionally, vomiting and diffuse abdominal pain. They occur in approximately 6% of patients treated with 5-FC[18]. Although these side effects are usually not severe; two cases of ulcerative colitis and bowel perforation have been reported[19]. Hepatotoxicity can occur during 5-FC treatment. In most cases it involves increases in serum concentrations of transaminases and alkaline phosphatase[20]. The incidence of hepatotoxicity is between 0 and 25%[20]. The most severe toxicity associated with 5-FC treatment are bone-marrow depression. There have been several reports of serious or life-threatening leucocytopenia, thrombocytopenia and/or pancytopenia[21-23]. The mechanism of toxicity of 5-FC is still not fully understood. It is likely that some of the side effects caused by 5-FC, for example hepatotoxicity and bone-marrow depression, are dose-dependent, although not all reports support this theory. Furthermore, it has been postulated that conversion of 5-FC to certain metabolites, especially 5-FU, could be one of the mechanisms of development of 5-FC-associated toxicity.

References

Heidelberg C, Chaudhuri NK, Danneberg P et al. Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature 1957; 179(4561): 663–666 Grunberg E, Titsworth E, Bennett M. Chemotherapeutic activity of 5-fluorocytosine. Antimicrob Agents Chemother 1963; 161:566–568 Tassel D, Madoff MA. Treatment of Candida sepsis and Cryptococcus meningitis with 5-fluorocytosine. A new antifungal agent. JAMA 1968; 206(4): 830–832 Benson JM, Nahata MC. Clinical use of systemic antifungal agents. Clin Pharm 1988; 7(6): 424–438 Scholer, H. J. (1980). Flucytosine. In Antifungal Chemotherapy, (Speller, D. C. E., Ed.), pp. 35–106. Wiley, Chichester. Waldorf AR, Polak A. Mechanisms of action of 5-fluorocytosine. Antimicrob Agents Chemother 1983; 23(1):79–85 Diasio RB, Bennett JE, Myers CE. Mode of action of 5-fluorocytosine. Biochem Pharmacol 1978; 27(5):703–707 Polak, A. & Scholer, H. J. (1975). Mode of action of 5-fluorocytosine and mechanisms of resistance. Chemotherapy 21, 113–30. Polak, A. (1977). 5-Fluorocytosine—current status with special references to mode of action and drug resistance. Contributions to Microbiology and Immunology 4, 158–67. Normark, S. & Sch?nebeck, J. (1973). In vitro studies of 5-fluorocytosine resistance in Candida albicans and Torulopsis glabrata. Antimicrobial Agents and Chemotherapy 2, 114–21. Fasoli, M. & Kerridge, D. (1988). Isolation and characterization of fluoropyrimidine-resistant mutants in two Candida species. Annals of the New York Academy of Sciences 544, 260–3. Francis, P. & Walsh, T. J. (1992). Evolving role of flucytosine in immunocompromised patients: new insights into safety, pharmacokinetics, and antifungal therapy. Clinical Infectious Diseases 15, 1003–18. Medoff, G. & Kobayashi, G. S. (1980). Strategies in the treatment of systemic fungal infections. New England Journal of Medicine 302, 145–55. Armstrong, D. & Schmitt, H. J. (1990). Older drugs. In Chemotherapy for Fungal Diseases, (Ryley, J. F., Ed.), pp. 439–54. Springer-Verlag, Berlin. Daneshmend, T. K. & Warnock, D. W. (1983). Clinical pharmacokinetics of systemic antifungal drugs. Clinical Pharmacokinetics 8, 17–42. Cutler, R. E., Blair, A. D. & Kelly, M. R. (1978). Flucytosine kinetics in subjects with normal and impaired renal function. Clinical Pharmacology and Therapeutics 24, 333–42. Block, E. R., Bennett, J. E., Livoti, L. G., Klein, W. J., MacGregor, R. R. & Henderson, L. (1974). Flucytosine and amphotericin B: hemodialysis effects on the plasma concentration and clearance. Studies in man. Annals of Internal Medicine 80, 613–7. Sch?nebeck, J., Polak, A., Fernex, M. & Scholer, H. J. (1973). Pharmacokinetic studies on the oral antimycotic agent 5-fluorocytosine in individuals with normal and impaired kidney function. Chemotherapy 18, 321–36. Benson, J. M. & Nahata, M. C. (1988). Clinical use of systemic antifungal agents. Clinical Pharmacy 7, 424–38. Bennet, J. E. (1977). Flucytosine. Annals of Internal Medicine 86, 319–21. Kauffman, C. A. & Frame, P. T. (1977). Bone marrow toxicity associated with 5-fluorocytosine therapy. Antimicrobial Agents and Chemotherapy 11, 244–7. Schlegel, R. J., Bernier, G. M., Bellanti, J. A., Maybee, D. A., Osborne, G. B., Stewart, J. L. et al. (1970). Severe candidiasis associated with thymic dysplasia, IgA deficiency, and plasma antilymphocyte effects. Pediatrics 45, 926–36. Meyer, R. & Axelrod, J. L. (1974). Fatal aplastic anemia resulting from flucytosine. Journal of the American Medical Association 228, 1573.

Description

5-Fluorocytosine (5-FC), a fluorinated pyrimidine analog, is a synthetic antimycotic prodrug that is converted by cytosine deaminase to 5-fluorouracil. 5-Fluorouracil, a widely used cytotoxic drug, is further metabolized to fluorinated ribo- and deoxyribonucleotides, resulting in the inhibition of DNA and protein synthesis, which has multiple effects including inhibition of Candida species and C. neoformans infections and cytotoxicity towards cancer cells. In combination with a retroviral replicating vector carrying a cytosine deaminase prodrug-activating gene, 5-FC has been shown to selectively eliminate CT26 and Tu-2449 tumor cells in vitro (IC50s = 4.2 and 1.5 μM, respectively) and to significantly improve survival and reduce tumor size (at a dose of 500 mg/kg) in two different syngeneic mouse glioma models.

Chemical Properties

White Crystalline Solid

Originator

Ancobon,Roche,US,1972

Uses

Different sources of media describe the Uses of 2022-85-7 differently. You can refer to the following data:
1. 5-Fluorocytosine acts as an antidiabetic, antifungal and antimicrobial agent. It is useful for the treatment of serious infections arises due to susceptible strains of Candida or Cryptococcus neoformans and chromomycosis. Further, it is employed in studies on TMP biosynthesis.
2. antidiabetic
3. antifungal and antimicrobial agent
4. 5-FC is a toxic antifungal/antimicrobial agent

Definition

ChEBI: An organofluorine compound that is cytosine that is substituted at position 5 by a fluorine. A prodrug for the antifungal 5-fluorouracil, it is used for the treatment of systemic fungal infections.

Indications

Flucytosine (Ancobon) is a synthetic, fluorinated pyrimidine that is structurally related to fluorouracil (FU) and floxuridine. It can be fungistatic and fungicidal. Although it is used more frequently in the treatment of systemic infections caused by Candida and Cryptococcus, dermatologic indications may include infections due to chromomycosis, sporotrichosis, Cladosporium, and Sporothrix species. It is generally ineffective against Aspergillus species.

Manufacturing Process

The preparation of 5-fluorouracil is given under "Fluorouracil." As described in US Patent 3,040,026, 5-fluorouracil is then subjected to the following steps to give flucytosine.Step 1: 2,4-Dichloro-5-Fluoropyrimidine - A mixture of 104 grams (0.8 mol) of 5-fluorouracil, 1,472 grams (9.6 mols) of phosphorus oxychloride and 166 grams (1.37 mols) of dimethylaniline was stirred under reflux for 2 hours. After cooling to room temperature, phosphorus oxychloride was removed by distillation at 18 to 22 mm and 22° to 37°C. The residue was then poured into a vigorously stirred mixture of 500 ml of ether and 500 gram of ice. After separating the ether layer, the aqueous layer was extracted with 500 ml, then 200 ml of ether. The combined ether fractions were dried over sodium sulfate, filtered, and the ether removed by vacuum distillation at 10° to 22°C. The residue, a yellow solid melting at 37° to 38°C, weighed 120 grams corresponding to a 90% yield. Vacuum distillation of 115 grams of this material at 74° to 80°C (16 mm) gave 108 grams of white solid melting at 38° to 39°C corresponding to an 84.5% yield.Step 2: 2-Chloro-4-Amino-5-Fluoropyrimidine - To a solution of 10.0 grams (0.06 mol) of 2,4-dichloro-5-fluoropyrimidine in 100 ml of ethanol, 25 ml of concentrated aqueous ammonia were slowly added. A slightly opalescent solution resulted. The temperature gradually rose to 35°C. The solution was then cooled in ice to 18°C and thereafter remained below 30°C. After three hours, a Volhard titration showed that 0.0545 mol of chlorine was present in ionic form. Storage in a refrigerator overnight resulted in some crystallization of ammonium chloride. A white sludge, resulting from the evaporation of the reaction mixture at 40°C, was slurried with 75 ml of water, filtered and washed free of chloride. After drying in vacuo, the product melted at 196.5° to 197.5°C, yield 6.44 grams. Evaporation of the mother liquors yielded a second crop of 0.38 gram, raising the total yield to 6.82 grams (79.3%).Step 3: 5-Fluorocytosine - A slurry of 34.0 grams (0.231 mol) of 2-chloro-4- amino-5-fluoropyrimidine in 231 ml of concentrated hydrochloric acid was heated in a water bath at 93° to 95°C for 125 minutes. The reaction was followed by means of ultraviolet spectrophotometry using the absorption at 245, 285, and 300 mμ as a guide. The absorption at 300 mμ rose to a maximum after 120 minutes and then dropped slightly. The clear solution was cooled to 25°C in an ice bath, then evaporated to dryness under vacuum at 40°C. After slurrying with water three times and reevaporating, the residue was dissolved in 100 milliliters of water. To this solution, cooled in ice, 29 ml of concentrated ammonia were added dropwise. The resulting precipitate was filtered, washed free of chloride with water, then with alcohol and ether. After drying in vacuo at 65°C, the product weighed 22.3 grams. An additional 6.35 grams was obtained by evaporation of the mother liquor, thus yielding a total of 28.65 grams (96.0%).

Brand name

Ancobon (Valeant).

Therapeutic Function

Antifungal

Antimicrobial activity

The spectrum of activity is restricted to Candida spp., Cryptococcus spp. and some fungi causing chromoblastomycosis.

Acquired resistance

About 2–3 of Candida spp. isolates (more in some centers) are resistant before treatment starts, and resistance may develop during treatment. The most common cause of resistance appears to be loss of the enzyme uridine monophosphate pyrophosphorylase.

General Description

Chemical structure: nucleoside

Pharmaceutical Applications

A synthetic fluorinated pyrimidine available for intravenous infusion or oral administration.

Biochem/physiol Actions

Nucleoside analog that has antifungal activities. 5-FC is deaminated by cytosine deaminase to product 5-fluorouracil, resulting in RNA miscoding. 5-Fluorocytosine inhibits DNA and RNA synthesis and interferes with ribosomal protein synthesis.

Mechanism of action

Flucytosine (5-flucytosine, 5-FC; Ancoban) is a fluorinated pyrimidine analogue of cytosine that was originally synthesized for possible use as an antineoplastic agent. 5-FC is converted to 5-fluorouracil inside the cell by the fungal enzyme cytosine deaminase. Subsequently, 5-FC metabolites interfere with fungal DNA synthesis by inhibiting thymidylate synthetase. Incorporation of these metabolites into fungal RNA may inhibit protein synthesis.

Pharmacokinetics

Oral absorption: Complete Cmax 25 mg/kg 6-hourly oral: 70–80 mg/L after 1–2 h Plasma half-life: 3–6 h Volume of distribution: 0.7–1 L/kg Plasma protein binding c. 12% Absorption is slower in persons with impaired renal function, but peak concentrations are higher. Levels in the CSF are around 75% of the simultaneous serum concentration. More than 90% of a dose of flucytosine is excreted in the urine in unchanged form. The serum half-life is much longer in renal failure, necessitating modification of the dosage regimen: for patients with a creatinine clearance below 40 mL/ min the dosage interval should be doubled to 12 h; in severe renal failure the dosage interval should be further increased to once daily or less, based on frequent serum drug concentration measurements.

Pharmacology

5-FC is well absorbed orally, with greater than 90% bioavailability. The serum half-life is 3 to 5 hours, with serum levels peaking 4 to 6 hours after a single dose.The drug is widely distributed in body fluids, with cerebrospinal fluid levels 60 to 80% of serum levels.The drug also penetrates well into urine, aqueous humor, and bronchial secretions.Minimal serum protein binding allows more than 90% of each dose to be excreted in the urine; significant dosage reductions are required in the presence of renal impairment. 5-FC can be removed by both hemodialysis and peritoneal dialysis. 5-FC conversion to toxic metabolites may occur in mammalian cells to a limited extent, which accounts for 5-FC toxicity.

Clinical Use

Different sources of media describe the Clinical Use of 2022-85-7 differently. You can refer to the following data:
1. 5-Fluorocytosine, 5-FC, 4-amino-5-fluoro-2(1H)-pyrimidinone, 2-hydroxy-4-amino-5-fluoropyrimidine (Ancobon). 5-Fluorocytosine is an orally active antifungal agent with a very narrow spectrum of activity. It is indicated only for the treatment of serious systemic infections caused by susceptible strains of Candida and Cryptococcus spp.The mechanism of action of 5-fluorocytosine (5-FC)has been studied in detail.The drug enters the fungal cell by active transport onATPases that normally transport pyrimidines. Once insidethe cell, 5-fluorocytosine is deaminated in a reaction catalyzedby cytosine deaminase to yield 5-fluorouracil(5-FU). 5-Fluorouracil is the active metabolite of the drug.5-Fluorouracil enters into pathways of both ribonucleotideand deoxyribonucleotide synthesis. The fluororibonucleotidetriphosphates are incorporated into RNA, causingfaulty RNA synthesis. This pathway causes cell death. Inthe deoxyribonucleotide series, 5-fluorodeoxyuridinemonophosphate (F-dUMP) binds to 5,10-methylenetetrahydrofolicacid, interrupting the one-carbon pool substratethat feeds thymidylate synthesis. Hence, DNA synthesisis blocked.
2. Flucytosine has significant antifungal activity against C. albicans, other Candida spp., C. neoformans, and the fungal organisms responsible for chromomycosis. Not considered the drug of choice for these fungal infections, 5-FC does remain useful as part of combination therapy for systemic candidiasis and cryptococcal meningitis and as an alternative drug for chromomycosis. When it is used as monotherapy, resistance and clinical failure are common. Potential mechanisms for drug resistance include decreased fungal cell membrane permeability and reduced levels of fungal cytosine deaminase. Combination therapy with amphotericin B and flucytosine in the treatment of cryptococcal meningitis and deep-seated Candida infections, such as septic arthritis and meningitis, permits reduced dosing of amphotericin B and prevents the emergence of 5-FC resistance. When higher doses of amphotericin B are used, combination therapy with 5-FC confers no additional clinical benefit except in the treatment of Candida endophthalmitis, where tissue penetration remains problematic.
3. Candidosis (in combination with amphotericin B or fluconazole) Cryptococcosis (in combination with amphotericin B or fluconazole) Monitoring of flucytosine concentrations is desirable in all patients, and mandatory in those with renal impairment.

Side effects

Different sources of media describe the Side effects of 2022-85-7 differently. You can refer to the following data:
1. Nausea, vomiting, abdominal pain and diarrhea are common. Serious side effects include myelosuppression and hepatic toxicity; they occur more frequently when serum concentrations exceed 100 mg/L. The nephrotoxic effects of amphotericin B can result in elevated blood concentrations of flucytosine, and levels of the latter drug should be monitored when these compounds are administered together.
2. When 5-FC is prescribed alone to patients with normal renal function, skin rash, epigastric distress, diarrhea, and liver enzyme elevations can occur.When it is prescribed to patients with renal insufficiency or to patients receiving concurrent amphotericin B therapy, blood levels of 5-FC may rise, and bone marrow toxicity leading to leukopenia and thrombocytopenia is common. 5-FC serum levels should be closely monitored in patients with renal insufficiency. Because of baseline leukopenia, 5-FC is often not tolerated by end-stage HIVinfected patients with disseminated fungal infection.

Synthesis

Flucytosine, 5-fluorocytosine (35.4.4), is synthesized from fluorouracil (30.1.3.3). Fluorouracil is reacted with phosphorous oxychloride in dimethylaniline to make 2,4-dichloro-5-fluoropyrimidine (35.4.2), which is reacted with ammonia to make a product substituted with chlorine at the fourth position of the pyrimidine ring—4-amino- 2-chloro-5-fluoropyrimidine (35.4.3). Hydrolysis of the chlorovinyl fragment of this compound in a solution of hydrochloric acid gives the desired flucytosine. An alternative way of synthesis consists of making flucytosine from a precursor of fluorouracil—5-fluoro-2-methylthiouracil (30.1.3.2) using a somewhat analogous scheme. Treating 5-fluoro-2-methylthiouracil (30.1.3.2) with phosphorous pentachloride gives 4-chloro-5-fluoro-2-methylthiopyrimidine (35.4.5), which upon being reacted with ammonium is transformed into 4-amino-5-fluoro-2-methylthiopyrimidine (35.4.6). Hydrolysis of the methylthiovinyl fragment using concentrated hydrobromic acid gives the desired flucytosine.

Drug interactions

Potentially hazardous interactions with other drugs Cytarabine: concentration of flucytosine possibly reduced.

Metabolism

Flucytosine itself is not cytotoxic but, rather, is a pro-drug that is taken up by fungi and metabolized to 5-fluorouracil (5-FU) by fungal cytidine deaminase. Then, 5-FU is converted to 5-fluorodeoxyuridine, which as a thymidylate synthase inhibitor interferes with both protein and RNA biosynthesis. 5-Fluorouracil is cytotoxic and is employed in cancer chemotherapy. Human cells do not contain cytosine deaminase and, therefore, do not convert flucytosine to 5-FU. Some intestinal flora, however, do convert the drug to 5-FU, so human toxicity does result from this metabolism.

Check Digit Verification of cas no

The CAS Registry Mumber 2022-85-7 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 2,0,2 and 2 respectively; the second part has 2 digits, 8 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 2022-85:
(6*2)+(5*0)+(4*2)+(3*2)+(2*8)+(1*5)=47
47 % 10 = 7
So 2022-85-7 is a valid CAS Registry Number.
InChI:InChI=1/C4H4FN3O/c5-8-2-1-3(6)7-4(8)9/h1-2H,(H2,6,7,9)

2022-85-7 Well-known Company Product Price

  • Brand
  • (Code)Product description
  • CAS number
  • Packaging
  • Price
  • Detail
  • TCI America

  • (F0321)  5-Fluorocytosine  >98.0%(HPLC)(T)

  • 2022-85-7

  • 1g

  • 80.00CNY

  • Detail
  • TCI America

  • (F0321)  5-Fluorocytosine  >98.0%(HPLC)(T)

  • 2022-85-7

  • 5g

  • 238.00CNY

  • Detail
  • TCI America

  • (F0321)  5-Fluorocytosine  >98.0%(HPLC)(T)

  • 2022-85-7

  • 25g

  • 710.00CNY

  • Detail
  • Alfa Aesar

  • (L16496)  5-Fluorocytosine, 98+%   

  • 2022-85-7

  • 250mg

  • 89.0CNY

  • Detail
  • Alfa Aesar

  • (L16496)  5-Fluorocytosine, 98+%   

  • 2022-85-7

  • 1g

  • 168.0CNY

  • Detail
  • Sigma-Aldrich

  • (F0175000)  Flucytosine  European Pharmacopoeia (EP) Reference Standard

  • 2022-85-7

  • F0175000

  • 1,880.19CNY

  • Detail
  • Sigma-Aldrich

  • (Y0001262)  Flucytosineforsystemsuitability  European Pharmacopoeia (EP) Reference Standard

  • 2022-85-7

  • Y0001262

  • 1,880.19CNY

  • Detail
  • USP

  • (1272000)  Flucytosine  United States Pharmacopeia (USP) Reference Standard

  • 2022-85-7

  • 1272000-200MG

  • 4,326.66CNY

  • Detail

2022-85-7SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 13, 2017

Revision Date: Aug 13, 2017

1.Identification

1.1 GHS Product identifier

Product name flucytosine

1.2 Other means of identification

Product number -
Other names 4-amino-5-fluoro-1,2-dihydropyrimidin-2-one

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

Emergency phone number -
Service hours Monday to Friday, 9am-5pm (Standard time zone: UTC/GMT +8 hours).

More Details:2022-85-7 SDS

2022-85-7Synthetic route

2,5-difluoro-4-chloro-pyrimidine
99429-06-8

2,5-difluoro-4-chloro-pyrimidine

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With ammonia In hydrogenchloride; ethanol; water98.1%
Cytosine
71-30-7

Cytosine

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
Stage #1: Cytosine With hydrogen fluoride at -15 - 0℃; Inert atmosphere;
Stage #2: at -20℃; for 4h; Inert atmosphere; Further stages;
95.7%
With 1,1,1,3',3',3'-hexafluoro-propanol; fluorine at 20℃; under 1125.11 Torr; Temperature; Pressure; Reagent/catalyst; Inert atmosphere;87.4%
With formic acid for 1.5h; Time; Flow reactor; Autoclave;63%
With formic acid; fluorine at 9℃; for 0.0833333h; Temperature; Concentration; Inert atmosphere;
4-amino-5-fluoro-2-methoxypyrimidine
1993-63-1

4-amino-5-fluoro-2-methoxypyrimidine

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With hydrogenchloride In methanol; water at 40 - 60℃;95%
With hydrogenchloride In water at 100℃; for 4h;57%
N-acetyl-5-bromocytosine
945548-37-8

N-acetyl-5-bromocytosine

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
Stage #1: N-acetyl-5-bromocytosine With acetamide; potassium fluoride In N,N-dimethyl-formamide at 130℃; for 5h; Inert atmosphere;
Stage #2: With ammonia In methanol at 40℃; for 12h; Reagent/catalyst; Solvent; Temperature;
93%
N-9-fluorenylmethoxycarbonyl-5-bromocytosine

N-9-fluorenylmethoxycarbonyl-5-bromocytosine

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
Stage #1: N-9-fluorenylmethoxycarbonyl-5-bromocytosine With potassium fluoride; tetrabutyl ammonium fluoride In N,N-dimethyl-formamide at 110℃; for 10h; Inert atmosphere;
Stage #2: With sodium hydroxide In 1,4-dioxane at 50℃; for 2h; Inert atmosphere;
91.1%
C7H12FNO2

C7H12FNO2

urea
57-13-6

urea

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
Stage #1: C7H12FNO2; urea With sodium methylate In 5,5-dimethyl-1,3-cyclohexadiene at 80℃; for 1.5h; Large scale;
Stage #2: With hydrogenchloride In water at 0 - 25℃; for 2h; pH=6; pH-value; Temperature; Large scale;
84.2%
5-fluoropyrimidine-2,4-diamine

5-fluoropyrimidine-2,4-diamine

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With sulfuric acid; water; sodium nitrite at 1 - 20℃; for 1.7h;83%
With sulfuric acid; sodium nitrite In water at 0 - 40℃;82%
Cytosine
71-30-7

Cytosine

A

Flucytosine
2022-85-7

Flucytosine

B

C4H5F2N3O2

C4H5F2N3O2

Conditions
ConditionsYield
With formic acid for 1.5h; Time; Flow reactor; Sealed tube;A 66%
B n/a
With formic acid; fluorine for 1.5h; Flow reactor; Overall yield = 64 %;
5-fluoro-2-(methylsulfonyl)pyrimidin-4-amine
1312324-60-9

5-fluoro-2-(methylsulfonyl)pyrimidin-4-amine

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With sodium hydroxide In 1,4-dioxane; water at 20℃; for 3h;66%
β-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine
134379-77-4

β-D-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine

A

(2-furyl)methyl alcohol
98-00-0

(2-furyl)methyl alcohol

B

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With acetic acid at 35 - 40℃; for 1h; pH=3 - 4; Product distribution; Further Variations:; pH-values; Temperatures;A 58%
B n/a
C4H4FN3O

C4H4FN3O

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With ammonium hydroxide at 70 - 80℃; for 3h; Autoclave; Large scale;52%
5-fluoro-2-(methylsulfanyl)pyrimidin-4-amine
1310078-72-8

5-fluoro-2-(methylsulfanyl)pyrimidin-4-amine

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With water; hydrogen bromide at 126℃; for 4h;51%
2-ethylsulfanyl-5-fluoro-pyrimidin-4-ylamine
701-87-1

2-ethylsulfanyl-5-fluoro-pyrimidin-4-ylamine

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With hydrogen bromide
With hydrogen bromide
Cytosine
71-30-7

Cytosine

A

Flucytosine
2022-85-7

Flucytosine

B

4-Difluoramino-cytosin

4-Difluoramino-cytosin

Conditions
ConditionsYield
With fluorine In water at 0℃; for 1h;
C7H8FN3O4

C7H8FN3O4

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With ammonia In methanol at 50℃; for 5h;26 g
C8H10FN3O4

C8H10FN3O4

Flucytosine
2022-85-7

Flucytosine

Conditions
ConditionsYield
With ammonia In methanol at 50℃; for 5h; Solvent; Large scale;2.67 kg
Flucytosine
2022-85-7

Flucytosine

benzoyl chloride
98-88-4

benzoyl chloride

N-benzoyl-5-fluorocytosine
10357-07-0

N-benzoyl-5-fluorocytosine

Conditions
ConditionsYield
With pyridine at 0 - 20℃; for 16h; Inert atmosphere;99%
Flucytosine
2022-85-7

Flucytosine

1-O-acetyl-5-O-(t-butyldiphenylsilyl)-2,3-dideoxy-2-fluoro-(L)-erythron-pentofuranose
202272-29-5

1-O-acetyl-5-O-(t-butyldiphenylsilyl)-2,3-dideoxy-2-fluoro-(L)-erythron-pentofuranose

(L)-5’-O-(t-butyldiphenylsilyl)-2’,3-dideoxy-2’-fluoro-5-fluorocytidine
202272-32-0

(L)-5’-O-(t-butyldiphenylsilyl)-2’,3-dideoxy-2’-fluoro-5-fluorocytidine

Conditions
ConditionsYield
Stage #1: Flucytosine With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane for 1h;
Stage #2: 1-O-acetyl-5-O-(t-butyldiphenylsilyl)-2,3-dideoxy-2-fluoro-(L)-erythron-pentofuranose With trimethylsilyl trifluoromethanesulfonate In 1,2-dichloro-ethane at 20℃; for 4h; Inert atmosphere;
99%
Flucytosine
2022-85-7

Flucytosine

pentyl chloroformate
638-41-5

pentyl chloroformate

(5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)carbamic acid amyl ester
862508-03-0

(5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)carbamic acid amyl ester

Conditions
ConditionsYield
With pyridine; tetrabutylammomium bromide In dichloromethane at 20℃; for 1.5h; Reagent/catalyst;96%
With pyridine In dichloromethane at -10 - 20℃; for 2h; Concentration; Inert atmosphere;94.3%
With pyridine75%
With tetra(n-butyl)ammonium hydrogensulfate; triethylamine In chloroform; water at 5 - 10℃; for 1h;300 g
Flucytosine
2022-85-7

Flucytosine

acrylonitrile
107-13-1

acrylonitrile

3-(5-fluoro-1-cytosinyl)propionitrile

3-(5-fluoro-1-cytosinyl)propionitrile

Conditions
ConditionsYield
In ammonia for 1h;95%
With triethylamine In water at 100℃; for 0.0833333h; Michael addition; microwave irradiation;84%
Flucytosine
2022-85-7

Flucytosine

potassium acesulfame
55589-62-3

potassium acesulfame

5-fluorocytosine acesulfame potassium

5-fluorocytosine acesulfame potassium

Conditions
ConditionsYield
In methanol at 45℃; Concentration; Temperature; Solvent;95%
Flucytosine
2022-85-7

Flucytosine

acrylic acid methyl ester
292638-85-8

acrylic acid methyl ester

methyl 3-(5-fluoro-1-cytosinyl)propionate

methyl 3-(5-fluoro-1-cytosinyl)propionate

Conditions
ConditionsYield
In ammonia for 1h;94%
Flucytosine
2022-85-7

Flucytosine

ethyl 5-bromovalerate
14660-52-7

ethyl 5-bromovalerate

C11H16FN3O3
1379471-11-0

C11H16FN3O3

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 1h;93.3%
Flucytosine
2022-85-7

Flucytosine

C22H28FN3O11

C22H28FN3O11

Conditions
ConditionsYield
With aluminum (III) chloride In dichloromethane at 5 - 10℃; for 2h;92.7%
Flucytosine
2022-85-7

Flucytosine

1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose
14215-97-5

1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose

1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5-fluorocytosine
53294-73-8

1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-5-fluorocytosine

Conditions
ConditionsYield
Stage #1: Flucytosine With 1,1,1,3,3,3-hexamethyl-disilazane In toluene for 3h; Heating;
Stage #2: 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose With trimethylsilyl trifluoromethanesulfonate In 1,2-dichloro-ethane at 20℃; for 8h;
91%
Flucytosine
2022-85-7

Flucytosine

2-amino-1,9-dihydro-6H-purin-6-one
73-40-5

2-amino-1,9-dihydro-6H-purin-6-one

copper(II) nitrate hydrate

copper(II) nitrate hydrate

water
7732-18-5

water

sodium hydroxide
1310-73-2

sodium hydroxide

[Cu2(5-fluorocytosine)(guanine)(OH)4(H2O)]*2H2O

[Cu2(5-fluorocytosine)(guanine)(OH)4(H2O)]*2H2O

Conditions
ConditionsYield
In ethanol; water byproducts: NaNO3; hydrated metal nitrate refluxed for about 10 hs in a mixt. of EtOH and triethyl orthoformate; 5-fluorocytozine and guanine added separately (molar ratio 2:1:1); mixt. refluxed for several hs; vol. reduced; pH adjusted to 7 (aq. NaOH soln.) with stirring; ppt. filtered; washed (EtOH, Et2O); oven-dried at 50-60°C; elem. anal.;91%
Flucytosine
2022-85-7

Flucytosine

(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-(methylcarbonyloxy)-1,3-oxathiolane-2-carboxylate
147027-09-6

(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-(methylcarbonyloxy)-1,3-oxathiolane-2-carboxylate

(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
764659-72-5

(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate

Conditions
ConditionsYield
Stage #1: (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-(methylcarbonyloxy)-1,3-oxathiolane-2-carboxylate With triethylsilane; iodine In dichloromethane at 0℃; for 1h; Inert atmosphere;
Stage #2: Flucytosine With N,O-bis-(trimethylsilyl)-acetamide In dichloromethane at 0 - 20℃; for 1h; Reagent/catalyst; Inert atmosphere; stereoselective reaction;
91%
Stage #1: Flucytosine With chloro-trimethyl-silane; 1,1,1,3,3,3-hexamethyl-disilazane at 25 - 130℃; Inert atmosphere;
Stage #2: (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-(methylcarbonyloxy)-1,3-oxathiolane-2-carboxylate With zirconium(IV) chloride In dichloromethane at 25 - 30℃; for 6h; Inert atmosphere;
80%
Flucytosine
2022-85-7

Flucytosine

acrylic acid ammonium salt

acrylic acid ammonium salt

3-(5-fluoro-1-cytosinyl)propionic acid

3-(5-fluoro-1-cytosinyl)propionic acid

Conditions
ConditionsYield
In ammonia for 4h;90%
Flucytosine
2022-85-7

Flucytosine

3,4,5-Trimethoxybenzoyl chloride
4521-61-3

3,4,5-Trimethoxybenzoyl chloride

N-(5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)-3,4,5-trimethoxybenzamide

N-(5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)-3,4,5-trimethoxybenzamide

Conditions
ConditionsYield
With pyridine at 100℃;90%
chloro-trimethyl-silane
75-77-4

chloro-trimethyl-silane

Flucytosine
2022-85-7

Flucytosine

=

=

Conditions
ConditionsYield
With 1,1,1,3,3,3-hexamethyl-disilazane In toluene at 100℃;90%
Flucytosine
2022-85-7

Flucytosine

2-amino-1,9-dihydro-6H-purin-6-one
73-40-5

2-amino-1,9-dihydro-6H-purin-6-one

zinc(II) nitrate hydrate

zinc(II) nitrate hydrate

water
7732-18-5

water

sodium hydroxide
1310-73-2

sodium hydroxide

[Zn2(5-fluorocytosine)(guanine)(OH)4(H2O)]*2H2O

[Zn2(5-fluorocytosine)(guanine)(OH)4(H2O)]*2H2O

Conditions
ConditionsYield
In ethanol; water byproducts: NaNO3; hydrated metal nitrate refluxed for about 10 hs in a mixt. of EtOH and triethyl orthoformate; 5-fluorocytozine and guanine added separately (molar ratio 2:1:1); mixt. refluxed for several hs; vol. reduced; pH adjusted to 7 (aq. NaOH soln.) with stirring; ppt. filtered; washed (EtOH, Et2O); oven-dried at 50-60°C; elem. anal.;89%
Flucytosine
2022-85-7

Flucytosine

C10H6BrF6NO
1215294-20-4

C10H6BrF6NO

C14H9F7N4O2
1215294-34-0

C14H9F7N4O2

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;89%
Flucytosine
2022-85-7

Flucytosine

(2R,3R,4R,5R)-2-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)-5-methyl-tetrahydrofuran-3,4-diyl diacetate
161599-46-8

(2R,3R,4R,5R)-2-(4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)-5-methyl-tetrahydrofuran-3,4-diyl diacetate

Conditions
ConditionsYield
With titanium tetrachloride In dichloromethane at 10 - 20℃; for 4h; Solvent;88.6%
Stage #1: Flucytosine With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane In toluene for 3h; Reflux;
Stage #2: 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribofuranose With tin(IV) chloride In dichloromethane at -5℃; Inert atmosphere; Heating;
83.6%
Stage #1: Flucytosine With trifluorormethanesulfonic acid; 1,1,1,3,3,3-hexamethyl-disilazane In acetonitrile for 2h; Reflux;
Stage #2: 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribofuranose With trifluorormethanesulfonic acid at 20 - 55℃;
80%
Flucytosine
2022-85-7

Flucytosine

1,2,3-tri-O-acetyl-α,β-D-ribofuranose-5-[phenylbis(isoamyl-L-aspartyl)]phosphate

1,2,3-tri-O-acetyl-α,β-D-ribofuranose-5-[phenylbis(isoamyl-L-aspartyl)]phosphate

2',3'-di-O-acetyl-5-fluorocytidine-5'-[phenylbis(isoamyl-L-aspartyl)]phosphate

2',3'-di-O-acetyl-5-fluorocytidine-5'-[phenylbis(isoamyl-L-aspartyl)]phosphate

Conditions
ConditionsYield
Stage #1: Flucytosine With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane for 4h; Vorbrueggen Nucleoside Synthesis; Reflux;
Stage #2: 1,2,3-tri-O-acetyl-α,β-D-ribofuranose-5-[phenylbis(isoamyl-L-aspartyl)]phosphate With tin(IV) chloride In 1,2-dichloro-ethane at 20℃; for 3h; Reagent/catalyst; Solvent; Vorbrueggen Nucleoside Synthesis; diastereoselective reaction;
88%
Flucytosine
2022-85-7

Flucytosine

2-bromo-N-(4-fluorophenyl)acetamide
2195-44-0

2-bromo-N-(4-fluorophenyl)acetamide

C12H10F2N4O2
1215294-23-7

C12H10F2N4O2

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;87%
Flucytosine
2022-85-7

Flucytosine

2-amino-1,9-dihydro-6H-purin-6-one
73-40-5

2-amino-1,9-dihydro-6H-purin-6-one

nickel(II) nitrate hydrate

nickel(II) nitrate hydrate

water
7732-18-5

water

sodium hydroxide
1310-73-2

sodium hydroxide

[Ni2(5-fluorocytosine)(guanine)(OH)4(H2O)]*2H2O

[Ni2(5-fluorocytosine)(guanine)(OH)4(H2O)]*2H2O

Conditions
ConditionsYield
In ethanol; water byproducts: NaNO3; hydrated metal nitrate refluxed for about 10 hs in a mixt. of EtOH and triethyl orthoformate; 5-fluorocytozine and guanine added separately (molar ratio 2:1:1); mixt. refluxed for several hs; vol. reduced; pH adjusted to 7 (aq. NaOH soln.) with stirring; ppt. filtered; washed (EtOH, Et2O); oven-dried at 50-60°C; elem. anal.;86%
2-bromo-N-(4-chloro-3-(trifluoromethyl)phenyl)acetamide

2-bromo-N-(4-chloro-3-(trifluoromethyl)phenyl)acetamide

Flucytosine
2022-85-7

Flucytosine

C13H9ClF4N4O2
1215294-09-9

C13H9ClF4N4O2

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;86%
Flucytosine
2022-85-7

Flucytosine

(4-acetoxy-1,3-dioxan-2-yl)methyl benzoate

(4-acetoxy-1,3-dioxan-2-yl)methyl benzoate

β-{4-[4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl]-1,3-dioxan-2-yl}methyl benzoate

β-{4-[4-amino-5-fluoro-2-oxopyrimidin-1(2H)-yl]-1,3-dioxan-2-yl}methyl benzoate

Conditions
ConditionsYield
Stage #1: Flucytosine With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane at 120℃; for 12h; Inert atmosphere;
Stage #2: (4-acetoxy-1,3-dioxan-2-yl)methyl benzoate With trimethylsilyl trifluoromethanesulfonate In dichloromethane at 0 - 20℃; Inert atmosphere; stereoselective reaction;
86%
Flucytosine
2022-85-7

Flucytosine

2-phenylimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde
127204-71-1

2-phenylimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde

C20H12FN5OS

C20H12FN5OS

Conditions
ConditionsYield
With acetic acid In ethanol for 24h; Reflux;85.1%
Flucytosine
2022-85-7

Flucytosine

C8H6BrClFNO
1215294-15-7

C8H6BrClFNO

C12H9ClF2N4O2
1215294-31-7

C12H9ClF2N4O2

Conditions
ConditionsYield
With potassium carbonate In N,N-dimethyl-formamide at 20℃;85%

2022-85-7Relevant articles and documents

One-Step Continuous Flow Synthesis of Antifungal WHO Essential Medicine Flucytosine Using Fluorine

Harsanyi, Antal,Conte, Annelyse,Pichon, Laurent,Rabion, Alain,Grenier, Sandrine,Sandford, Graham

, p. 273 - 276 (2017)

In Africa around 625-000 mortalities per annum (20% of HIV/AIDS related deaths) are due to the affects of the Cryptococcal meningitis (CM) fungal infection. Recently, the World Health Organisation (WHO) and the Infectious Disease Society of America (IDSA) recommended that the first line treatment for CM is a combination of amphotericin B and flucytosine, both now WHO Essential Medicines. However, flucytosine is not even registered for use in any African nation due, in part, to its relatively high cost of manufacture and lack of generic manufacturers. Currently, flucytosine is manufactured by an expensive four-step manufacturing process. Here we report a one-step continuous flow process involving the reaction of inexpensive cytosine with fluorine gas using stainless steel tubular laboratory and pilot-scale silicon carbide reactor devices which is readily scaleable to a manufacturing process with a low initial capital expenditure.

2-CYANO-2-FLUOROETHENOLATE SALTS (CFES): VERSITILE ACTIVE PHARMACEUTICAL INTERMEDIATES

-

Paragraph 0011, (2020/08/30)

The present invention relates to new enolate structures with utility as active pharmaceutical intermediates for the preparation of efficacious drugs such as those derived from 5-fluorocytosine (5-FC).

Preparation method of 5-fluorocytosine

-

Paragraph 0038; 0056-0080; 0082; 0087-0097; 0099; 0104-0115, (2019/10/01)

The invention provides a preparation method of 5-fluorocytosine. The method is characterized by including the following steps that 1, an organic solvent, fluoroacetonitrile, ethyl formate and organicbase are added into an autoclave for a heating reaction in a predetermined gaseous environment, then decompressing and cooling are conducted, and first reaction liquid containing an intermediate 1 isobtained; 2, an alcohol solution of hydrogen chloride is added into a reaction still, the first reaction liquid is added for reaction after cooling, a second reaction liquid is obtained after reaction, water is added into the second reaction liquid, the pH value is adjusted to be 6-8, a first organic layer is obtained after standing, and the first organic layer is distilled to obtain an intermediate 2; 3, the intermediate 2 and urea are subjected to an aldimine condensation reaction, and then a crude product of 5-fluorocytosine is obtained. According to the method, the synthesis process is simple, there are a few required reaction steps, the total yield is relatively high, the safety of reaction is high, the production efficiency is improved, and the production cost is reduced.

Method for synthesizing 5-flucytosine

-

Paragraph 0063; 0067, (2018/03/25)

The invention discloses a method for synthesizing 5-flucytosine and belongs to the field of organic chemistry. The method comprises the following reaction steps of: adopting fluoroacetonitrile as a raw material, firstly reacting with N,N-dimethyl formamide dimethylacetal to generate 2-fluoro-3-dimethylaminoacrylonitrile, then reacting with urea to obtain an intermediate, and then under the existence of alkali, carrying out cyclization reaction to generate the 5-flucytosine. The method disclosed by the invention has the beneficial effects that the whole process only needs three step reactions,the reaction steps are short, the operation is easy, the use of dangerous chemicals such as fluorine gas and the like is avoided, the total yield reaches not less than 50%, so that the method is suitable for industrial large-scale production.

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