69-74-9

Basic information

• Product Name: 1-beta-D-Arabinofuranosylcytosine hydrochloride
• Synonyms: 4-amino-1-[3,4-dihydroxy-5-(hydroxymethyl)-2-tetrahydrofuranyl]-2-pyrimidinone;4-amino-1-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2(1H)-one;4-amino-1-[3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]pyrimidin-2-one;-D-arabinofuranoside hydrochloride;Cytosine β4-Amino-1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)-tetrahydrofuran-2-yl)pyrimidin-2(1H)-;Cytosine-beta-D-arabinofuranose hydrochloride;1-beta-d-arabinofuranosylcytosinemonohydrochloride
• CAS NO: 69-74-9
• Molecular Formula: C₉H₁₃N₃O₅*ClH
• Molecular Weight: 279.68
• EINECS: 200-713-9
• Product Categories: Pyridines, Pyrimidines, Purines and Pteredines
• Mol File: 69-74-9.mol
• Article Data: 4

Chemical Properties

• Melting Point: 197-198 °C(lit.)
• Boiling Point: 545.7 °C at 760 mmHg
• Flash Point: 283.8 °C
• Appearance: White to off-white/crystalline
• Vapor Pressure: 3.5E-14mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: insoluble in EtOH; ≥14.2 mg/mL in DMSO; ≥64.2 mg/mL in H2O
• Stability: Stable. Combustible. Incompatible with strong oxidizing agents.
• CAS DataBase Reference: 1-beta-D-Arabinofuranosylcytosine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: 1-beta-D-Arabinofuranosylcytosine hydrochloride(69-74-9)
• EPA Substance Registry System: 1-beta-D-Arabinofuranosylcytosine hydrochloride(69-74-9)

Safety Data

• Hazard Codes: Xn
• Statements: 36-43-63
• Safety Statements: 26-36/37
• WGK Germany: 3
• RTECS: HA5500000
• HazardClass: IRRITANT
• Hazardous Substances Data: 69-74-9(Hazardous Substances Data)

Usage

Description

Cytosine beta-D-arabinofuranoside Hydrochloride is the salt form of Cytarabine, which is a selective inhibitor of DNA synthesis and is used as an antineoplastic and antiviral. Cytosine beta-D-arabinofuranoside Hydrochloride is used in chemotherapy for the treatment of white blood cells cancers such as acute myeloid leukemia (AML) and non-Hodgkin lymphoma.

Chemical Properties

Crystalline

Uses

Different sources of media describe the Uses of 69-74-9 differently. You can refer to the following data:
1. Antiviral.
2. Interferes with the synthesis of DNA

Therapeutic Function

Cancer chemotherapy

General Description

Crystals (from aqueous ethanol) or fluffy white powder.

Air & Water Reactions

Water soluble. Hydrolysis occurs readily, especially with acid.

Reactivity Profile

1-beta-D-Arabinofuranosylcytosine hydrochloride undergoes decomposition in acidic solutions.

Fire Hazard

Flash point data for 1-beta-D-Arabinofuranosylcytosine hydrochloride are not available; however, 1-beta-D-Arabinofuranosylcytosine hydrochloride is probably combustible.

Biological Activity

cytarabine hydrochloride is an effective drug in the treatment of cancers of white blood cells [1].cytarabine hydrochloride is a dxoxycytidine (dc) analogue. cytarabine hydrochloride has been found to be phosphorylated into a triphophate form, and thus compete with dctp for incorporation into dna. cytarabine hydrochloride has reported to incorporate into dna and block dna synthesis by inhibiting the function of dna and rna polymerases. in addition, incorporated has shown a growth inhibition dose-dependent curve using acute myelogenous leukemia (aml) in a growth inhibition assay with ic50 values of 16nm,103μm and 223μm for ccrf-cem, cem/arac8c and cem/dck-cell lines, respectively. moreover, cytarabine hydrochloride has been exhibited to retrovirally transducer rat leukemic ka cells by wst-1 assay with ic50 values of 0.69μm,1.73μm and 0.037μm for ka, ka/gfp and ka/wt, respectively [1,2].

Biochem/physiol Actions

Ara-C is phosphorylated to Ara-CTP and is incorporatee into DNA. It inhibits DNA replication by forming cleavage complexes with topoisomerase I resulting in DNA fragmentation, and ultimately induces apoptosis via the PKC signaling pathway. Does not inhibit RNA synthesis. Anti-leukemia agent.

Safety Profile

Poison by intravenous route.Moderately toxic by intraperitoneal and subcutaneousroutes. Experimental reproductive effects. A human eyeirritant. Mutation data reported. When heated todecomposition it emits very toxic fumes of NOx and HCl.

references

[1] tobias sc1, borch rf.synthesis and biological evaluation of a cytarabine phosphoramidate prodrug. mol pharm. 2004 mar-apr; 1(2):112-6.[2] veuger mj1, heemskerk mh, honders mw, willemze r, barge rm.functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells. blood. 2002 feb 15; 99(4):1373-80.

InChI:InChI=1/C9H13N3O5.ClH/c10-5-1-2-12(9(16)11-5)8-7(15)6(14)4(3-13)17-8;/h1-2,4,6-8,13-15H,3H2,(H2,10,11,16);1H

Synthetic route

arabinosyl cytosine (147-94-4) → cytarabine hydrochloride (69-74-9)

Conditions	Yield
With hydrogenchloride In methanol at 2 - 25℃; for 4h;	96%
With hydrogenchloride In diethyl ether

ancitabine hydrochloride (10212-25-6) → cytarabine hydrochloride (69-74-9)

Conditions	Yield
With ammonia In water at 80℃; for 0.5h; Temperature;	62.4%

cytarabine hydrochloride (69-74-9) + 3-Acryloylamino-propionic acid pentafluorophenyl ester (219797-98-5) → N-{2-[1-((2R,3S,4S,5R)-3,4-Dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-4-ylcarbamoyl]-ethyl}-acrylamide (186594-89-8)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane In pyridine at 80℃;	95%

cytarabine hydrochloride (69-74-9) → 4-amino-5-chloro-1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidine-2(1H)-one (17676-65-2)

Conditions	Yield
With hydrogenchloride; 3-chloro-benzenecarboperoxoic acid In N,N-dimethyl acetamide for 1h; Ambient temperature;	83.9%

cytarabine hydrochloride (69-74-9) + 4-Acryloylamino-butyric acid pentafluorophenyl ester (219797-99-6) → N-(3-(N4-carbamoyl-1-(β-D-arabinofuranosyl)cytosine)-propyl)acrylamide (186594-93-4)

Conditions	Yield
With 1,4-diaza-bicyclo[2.2.2]octane In pyridine at 80℃;	78%

elaidoyl chloride (112-77-6, 7378-94-1, 7459-35-0) + cytarabine hydrochloride (69-74-9) → elacytarabine

Conditions	Yield
In ISOPROPYLAMIDE at 30℃; for 22h;	72%

cytarabine hydrochloride (69-74-9) + gondoic acid chloride → CP-4057

Conditions	Yield
In ISOPROPYLAMIDE; N,N-dimethyl-formamide at 25℃; for 24h;	66%

N-(2-(4-chlorophenyl)-3-(2-(dipropylamino)-2-oxoethyl)imidazo[1,2-a]pyridin-8-yl)-6-oxo-6-(2-thioxothiazolidin-3-yl)hexanamide (1257411-82-7) + cytarabine hydrochloride (69-74-9) → N1-(2-(4-chlorophenyl)-3-(2-(dipropylamino)-2-oxoethyl)imidazo[1,2-a]pyridin-8-yl)-N6-(1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)adipamide (1257411-83-8)

Conditions	Yield
With pyridine at 50℃;	66%

cytarabine hydrochloride (69-74-9) + 2-(6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)acetic acid (82626-74-2) → 2-(6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-N-(1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)acetamide (1257411-86-1)

Conditions	Yield
Stage #1: 2-(6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)acetic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.25h; Inert atmosphere; Stage #2: cytarabine hydrochloride In N,N-dimethyl-formamide Inert atmosphere;	65%

2-(pyridin-2-yldisulfaneyl)ethyl 1H-1,2,4-triazole-1-carboxylate + cytarabine hydrochloride (69-74-9) → 2-(pyridin-2-yldisulfaneyl)ethyl (1-((3S,4S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)carbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2h;	63%

mono (2,2,2-trichloroethyl) azelaoyl chloride + cytarabine hydrochloride (69-74-9) → 5'-O-[(2,2,2-trichloroethyl)-azelaoyl]-1-β-D-arabinofuranosyl-cytosine (879015-37-9)

Conditions	Yield
In DMA at 20℃;	56.7%

cytarabine hydrochloride (69-74-9) + Hexanoyl chloride (142-61-0) → C15H23N3O6

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 24h;	55%

cytarabine hydrochloride (69-74-9) + n-octanoic acid chloride (111-64-8) → 4-amino-1-(O5-octanoyl-β-D-arabinofuranosyl)-1H-pyrimidin-2-one (31088-08-1)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 24h;	55%

cytarabine hydrochloride (69-74-9) → (4S)-5'-O-cis-[4-(pyridin-4yl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside (685111-92-6)

Conditions	Yield
Stage #1: (-)-(S)-1-(pyridin-4-yl)-1,3-propanediol With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; trichlorophosphate In pyridine; acetonitrile at -17 - 42℃; for 3.6h; Stage #2: cytarabine hydrochloride In pyridine; acetonitrile at 4 - 6℃; for 88h;	48%

di-tert-butyl dicarbonate (24424-99-5) + cytarabine hydrochloride (69-74-9) → tert-butyl 1-((2R,3S,4R,5R)-3,4-bis(tert-butoxycarbonyloxy)-5-((tert-butoxycarbonyloxy)-methyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-ylcarbamate + C24H37N3O11 (1257411-75-8)

Conditions	Yield
With potassium hydroxide In 1,4-dioxane; water at 20℃; for 17h;	A 15% B 48%

cytarabine hydrochloride (69-74-9) + butyryl chloride (141-75-3) → C13H19N3O6 (917898-23-8)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 24h;	42%

propionyl chloride (79-03-8) + cytarabine hydrochloride (69-74-9) → 5'-O-propionyl ara-C (881848-60-8)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 24h;	39%

cytarabine hydrochloride (69-74-9) + n-decanoyl chloride (112-13-0) → 4-amino-1-(O5-decanoyl-β-D-arabinofuranosyl)-1H-pyrimidin-2-one (58611-44-2)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 24h;	31%

cytarabine hydrochloride (69-74-9) + acetyl chloride (75-36-5) → 4-amino-1-(O5-acetyl-β-D-arabinofuranosyl)-1H-pyrimidin-2-one (31088-09-2)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 24h;	27%

(4S)-(-)-trans-(4-pyridyl)-2-chloro-2-oxo-1,3,2-dioxaphosphorinane + cytarabine hydrochloride (69-74-9) → (4S)-5'-O-cis-[4-(pyridin-4yl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside (685111-92-6)

Conditions	Yield
Stage #1: (4S)-(-)-trans-(4-pyridyl)-2-chloro-2-oxo-1,3,2-dioxaphosphorinane; cytarabine hydrochloride With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone In acetonitrile at 20 - 35℃; for 48h; Stage #2: With methanol In acetonitrile at 20℃; for 2h;	26%

cytarabine hydrochloride (69-74-9) + [2-(4-chlorophenyl)-6,8-dichloroimidazo[1,2-a]pyridin-3-yl]acetic acid (362512-44-5) → 2-(6,8-dichloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-N-(1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)acetamide (1257411-84-9)

Conditions	Yield
Stage #1: [2-(4-chlorophenyl)-6,8-dichloroimidazo[1,2-a]pyridin-3-yl]acetic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.25h; Inert atmosphere; Stage #2: cytarabine hydrochloride In N,N-dimethyl-formamide Inert atmosphere;	25%

cytarabine hydrochloride (69-74-9) + (6,8-Dichloro-2-phenyl-imidazo[1,2-a]pyridin-3-yl)-acetic acid (573704-25-3) → 2-(6,8-dichloro-2-(phenyl)imidazo[1,2-a]pyridin-3-yl)-N-(1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)acetamide (1257411-85-0)

Conditions	Yield
Stage #1: (6,8-Dichloro-2-phenyl-imidazo[1,2-a]pyridin-3-yl)-acetic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide at 20℃; for 0.25h; Inert atmosphere; Stage #2: cytarabine hydrochloride In N,N-dimethyl-formamide Inert atmosphere;	23%

methyl 9-chloro-9-oxononanoate (56555-02-3) + cytarabine hydrochloride (69-74-9) → 1-(5-O-azelayl-β-D-arabinofuranosyl)cytosine methyl ester (848046-38-8)

Conditions	Yield
Stage #1: methyl 9-chloro-9-oxononanoate; cytarabine hydrochloride In 2,4-dichlorophenoxyacetic acid dimethylamine at 20℃; Stage #2: With triethylamine	21.6%

cytarabine hydrochloride (69-74-9) + benzyl chloroformate (501-53-1) → benzyl 1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-ylcarbamate (170935-63-4)

Conditions	Yield
With potassium hydrogencarbonate In water; ethyl acetate at 80℃; for 16h;	15%

acetic anhydride (108-24-7) + cytarabine hydrochloride (69-74-9) → N4-acetyl-1-<2',3',5'-tri-O-acetyl-β-D-arabinofuranosyl>cytosine (6742-08-1)

Conditions	Yield
With pyridine at 45℃; for 18h;	129 g

chloro-trimethyl-silane (75-77-4) + cytarabine hydrochloride (69-74-9) → 4-Amino-1-((2R,3S,4R,5R)-3,4-bis-trimethylsilanyloxy-5-trimethylsilanyloxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (51432-43-0)

Conditions	Yield
With pyridine at 20℃; for 1h;

cytarabine hydrochloride (69-74-9) → 1-(β-D-arabinofuranosyl)-N4-benzoylcytosine (16640-05-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: pyridine / 1 h / 20 °C 2: pyridine / 4 h / 20 °C 3: aq. NH4OH / 0.25 h / 20 °C View Scheme

cytarabine hydrochloride (69-74-9) → N-[1-((2R,3S,4R,5R)-3,4-Bis-trimethylsilanyloxy-5-trimethylsilanyloxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-4-yl]-benzamide

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine / 1 h / 20 °C 2: pyridine / 4 h / 20 °C View Scheme

cytarabine hydrochloride (69-74-9) → 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)cytosine (6742-07-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 129 g / pyridine / 18 h / 45 °C 2: ZnBr2 / CHCl3; methanol / Ambient temperature View Scheme

Upstream product

• 10212-25-6 ancitabine hydrochloride 
• 147-94-4 arabinosyl cytosine 

Downstream Products

• 6742-08-1 N⁴,2',3',5'-O-tetra-acetylarabinosylcytosine 
• 17676-65-2 1-β-D-arabinofuranosyl-5-chlorocytosine 
• 685111-92-6 (4S)-5'-O-cis-[4-(pyridin-4yl)-2-oxido-1,3,2-dioxaphosphorinan-2yl]-cytosine-β-D-arabinofuranoside 
• 31088-08-1 5'-Octanoyl-ara-cytidin 
• 1257411-85-0 2-(6,8-dichloro-2-(phenyl)imidazo[1,2-a]pyridin-3-yl)-N-(1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)acetamide 
• 1257411-86-1 2-(6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-N-(1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)acetamide 
• 1257411-84-9 2-(6,8-dichloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-N-(1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)acetamide 
• 1257411-77-0 C₃₉H₄₄Cl₃N₅O₁₂ 
• 1257411-76-9 ((2R,3R,4S,5R)-5-(4-(tert-butoxycarbonylamino)-2-oxopyrimidin-1(2H)-yl)-3,4-bis(tert-butoxycarbonyloxy)-tetrahydrofuran-2-yl)methyl 2-(6,8-dichloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)acetate 
• 1257411-83-8 N₁-(2-(4-chlorophenyl)-3-(2-(dipropylamino)-2-oxoethyl)imidazo[1,2-a]pyridin-8-yl)-N₆-(1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-yl)adipamide 
• 1257411-79-2 4-(6,8-dichloro-3-(2-(dipropylamino)-2-oxoethyl)imidazo[1,2-a]pyridin-2-yl)phenyl 1-((2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-ylcarbamate 
• 6742-07-0 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)cytosine 
• 16640-05-4 1-(β-D-arabinofuranosyl)-N⁴-benzoylcytosine 
• 170935-63-4 benzyl 1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-2-oxo-1,2-dihydropyrimidin-4-ylcarbamate 

Relevant articles and documents

Preparation method of cytarabine hydrochloride

The invention provides a preparation method of cytarabine hydrochloride. The preparation method comprises following steps: A, cytidine and acetylsalicyl chloride are reacted so as to obtain acetyl cyclocytidine; B, acetyl cyclocytidine is subjected to deprotection in a hydrochloric acid methanol solution so as to obtain cyclocytidine hydrochloride; and C, cyclocytidine hydrochloride is subjected to ring-opening reaction so as to obtain cytarabine hydrochloride. The preparation method of cytarabine hydrochloride possesses following advantages: the raw materials are cheap and easily available; using of high toxicity substances difficult to remove is avoided; the preparation method is safe, and is friendly to the environment; and product yield and purity are high.

Novel cytarabine monophosphate prodrugs

Compounds of Formula I, their preparation and uses are described: wherein: M and V are cis to one another and MH is cytarabine; the 5′ oxygen of said cytarabine is attached to the phosphorus; V is 4-pyridyl; and pharmaceutically acceptable prodrugs and salts thereof.