119804-96-5

Basic information

• Product Name: 2'-methyl-2'-deoxyidenecytidine
• Synonyms: 2'-methyl-2'-deoxyidenecytidine
• CAS NO: 119804-96-5
• Molecular Formula: C₁₀H₁₃N₃O₄
• Molecular Weight: 239.22792
• Mol File: 119804-96-5.mol
• Article Data: 5

Chemical Properties

• Melting Point: 190-194 °C (decomp)(Solv: water (7732-18-5))
• Boiling Point: 494.8°Cat760mmHg
• Flash Point: 253.1°C
• Appearance: /
• Density: 1.63g/cm³
• PKA: 13.29±0.60(Predicted)
• CAS DataBase Reference: 2'-methyl-2'-deoxyidenecytidine(CAS DataBase Reference)
• NIST Chemistry Reference: 2'-methyl-2'-deoxyidenecytidine(119804-96-5)
• EPA Substance Registry System: 2'-methyl-2'-deoxyidenecytidine(119804-96-5)

Safety Data

• Hazardous Substances Data: 119804-96-5(Hazardous Substances Data)

Usage

General Description

2'-Methyl-2'-deoxyidenecytidine, also known as MDIC, is a synthetic chemical compound that is commonly used in the field of nucleic acid research and drug development. It is a modified nucleoside analog with a methyl group attached to the 2' carbon of the ribose sugar, which gives it increased stability and resistance to degradation by nucleases. MDIC has been studied for its potential antiviral activity, as well as its ability to inhibit DNA and RNA synthesis. It has also been evaluated for its potential use in cancer therapy, as it can disrupt the replication of cancer cells. Its unique structure and functional properties make it a valuable tool for studying nucleic acid biochemistry and for developing novel pharmaceuticals.

Synthetic route

3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2'-deoxy-2'-methylidenecytidine (130954-04-0) → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
With n-Bu4F In tetrahydrofuran for 1.5h; Ambient temperature;	92%
With tetrabutyl ammonium fluoride In tetrahydrofuran for 2h; Yield given;

4-ethoxy-(2-deoxy-2'-methylidene-β-D-ribofuranosyl)-2-(1H)-pyrimidinone (113648-24-1) → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
With ammonia In methanol at 100℃; for 48h;	81%

3',5'-bis-O-tert-butyldimethylsilyl-2'-deoxy-2'-methylidenecytidine (534605-37-3) → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran for 2h; Yield given;

N4-benzoyl-1-[2-deoxy-2-methylidene-3,5-di-O-benzoyl-β-D-glycero-pentofuranosyl]cytosine → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
With ammonia In methanol at 20℃;

4-etoxy-1-<2-deoxy-2-methylidene-3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl>-2-(1H)-pyrimidinone (113648-23-0) → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 91 percent / tetra-n-butylammonium fluoride / tetrahydrofuran 2: 81 percent / ammonia / methanol / 48 h / 100 °C View Scheme

4-ethoxy-1-<3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-erythro-2-pentulofuranosyl>-2(1H)-pyrimidinone (113648-22-9) → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 41 percent 2: 91 percent / tetra-n-butylammonium fluoride / tetrahydrofuran 3: 81 percent / ammonia / methanol / 48 h / 100 °C View Scheme

1-((6aR,8R,9aS)-2,2,4,4-tetraisopropyl-9-methylenetetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)-pyrimidine-2,4(1H,3H)-dione (102789-14-0) → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 99 percent / POCl3, triethylamine / acetonitrile / 2 h / Ambient temperature 2: 30 percent aq. NH3 / dioxane / 12 h / Ambient temperature 3: tetrabutylammonium fluoride / tetrahydrofuran / 2 h View Scheme
Multi-step reaction with 3 steps 1: 77 percent / 4-chlorophenyl phosphorodichloridate, pyridine / 48 h / Ambient temperature 2: NH4OH / dioxane / Ambient temperature 3: 92 percent / n-Bu4F / tetrahydrofuran / 1.5 h / Ambient temperature View Scheme

1-<3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2-deoxy-2-methylidene-β-D-ribofuranosyl>-4-(1,2,4-triazol-1-yl)-1H-pyrimidin-2-one (134660-28-9) → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 30 percent aq. NH3 / dioxane / 12 h / Ambient temperature 2: tetrabutylammonium fluoride / tetrahydrofuran / 2 h View Scheme
Multi-step reaction with 2 steps 1: NH4OH / dioxane / Ambient temperature 2: 92 percent / n-Bu4F / tetrahydrofuran / 1.5 h / Ambient temperature View Scheme

1-((2R,5R)-4-((tert-butyldimethylsilyl)oxy)-5-((tert-butyldimethylsilyl)oxy)tetrahydrofuran-2-yl)pyrimidine-2,4 (1H,3H)-dione (134660-24-5) → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 99 percent / POCl3, triethylamine / acetonitrile / 2 h / Ambient temperature 2: 30 percent aq. NH3 / dioxane / 12 h / Ambient temperature 3: tetrabutylammonium fluoride / tetrahydrofuran / 2 h View Scheme

1-[(2R,4S,5R)-4-(tert-Butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-3-methylene-tetrahydro-furan-2-yl]-4-[1,2,4]triazol-1-yl-1H-pyrimidin-2-one (134660-27-8) → 2'-deoxy-2'-methylenecytidine (119804-96-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 30 percent aq. NH3 / dioxane / 12 h / Ambient temperature 2: tetrabutylammonium fluoride / tetrahydrofuran / 2 h View Scheme

2'-deoxy-2'-methylenecytidine (119804-96-5) + α-[2-(trimethylsilyl)ethoxy]-2-N-[2-(trimethylsilyl)ethoxycarbonyl]folic acid (292045-47-7) → 1-(2-deoxy-2-methylene-β-D-erythro-pentofuranosyl)-4-N-[γ-[α-[2-(trimethylsilyl)ethoxy]-2-N-[2-(trimethylsilyl)ethoxycarbonyl]folyl]]cytosine (292045-54-6)

Conditions	Yield
With triethylamine; isobutyl chloroformate In N,N-dimethyl-formamide at 20℃; for 2h; Substitution;	66%

concentrated ammonia water + 2'-deoxy-2'-methylenecytidine (119804-96-5) + n-decanoyl chloride (112-13-0) → 2'-DEOXY-2'-METHYLIDENE-N4-DECANOYLCYTIDINE (130674-50-9)

Conditions	Yield
With chloro-trimethyl-silane In pyridine; water	45.6%

chloro-trimethyl-silane (75-77-4) + concentrated ammonia water + 2'-deoxy-2'-methylenecytidine (119804-96-5) + Stearoyl chloride (112-76-5) → 2'-DEOXY-2'-METHYLIDENE-N4-STEAROYLCYTIDINE (130674-49-6)

Conditions	Yield
In pyridine; water	39.6%

2'-deoxy-2'-methylenecytidine (119804-96-5) → 1-(2-deoxy-2-methylene-β-D-erythro-pentofuranosyl)cytosine 5'-monophosphate

Conditions	Yield
With triethyl phosphate; trichlorophosphate at 5℃; for 1h;	30%

dipalmitoylphosphatidylcholine (35418-55-4) + 2'-deoxy-2'-methylenecytidine (119804-96-5) → 5'-phosphatidyl-2'-deoxy-2'-methylenecytidine

Conditions	Yield
With sodium acetate buffer; Dianion WK-20 resin (Na(1+) form); phospholipase D 1.) CHCl3, 40 deg C, 6 h; Yield given. Multistep reaction;

2'-deoxy-2'-methylenecytidine (119804-96-5) → C29H49N3O10P(1-)*Na(1+)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1.) phospholipase D, sodium acetate buffer (pH 4.5), 2.) Dianion WK-20 resin (Na(1+) form) / 1.) CHCl3, 40 deg C, 6 h 2: aq. sodium deoxycholate, phospholipase A2, CaCl2, 3,3-dimethylglutarate-NaOH buffer (pH 7.0) / 37 °C View Scheme

Upstream product

• 134660-27-8 1-[(2R,4S,5R)-4-(tert-Butyl-dimethyl-silanyloxy)-5-(tert-butyl-dimethyl-silanyloxymethyl)-3-methylene-tetrahydro-furan-2-yl]-4-[1,2,4]triazol-1-yl-1H-pyrimidin-2-one 
• 134660-24-5 1-((2R,5R)-4-((tert-butyldimethylsilyl)oxy)-5-((tert-butyldimethylsilyl)oxy)tetrahydrofuran-2-yl)pyrimidine-2,4 (1H,3H)-dione 
• 134660-28-9 1-<3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2-deoxy-2-methylidene-β-D-ribofuranosyl>-4-(1,2,4-triazol-1-yl)-1H-pyrimidin-2-one 
• 102789-14-0 1-((6aR,8R,9aS)-2,2,4,4-tetraisopropyl-9-methylenetetrahydro-6H-furo[3,2-f][1,3,5,2,4]trioxadisilocin-8-yl)-pyrimidine-2,4(1H,3H)-dione 
• 113648-22-9 4-ethoxy-1-<3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-β-D-erythro-2-pentulofuranosyl>-2(1H)-pyrimidinone 
• 113648-23-0 4-etoxy-1-<2-deoxy-2-methylidene-3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-ribofuranosyl>-2-(1H)-pyrimidinone 
• 863329-63-9 N⁴-benzoyl-1-[2-deoxy-2-methylidene-3,5-di-O-benzoyl-β-D-glycero-pentofuranosyl]cytosine 
• 534605-37-3 3',5'-bis-O-tert-butyldimethylsilyl-2'-deoxy-2'-methylidenecytidine 
• 130954-04-0 3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2'-deoxy-2'-methylidenecytidine 
• 113648-24-1 4-ethoxy-(2-deoxy-2'-methylidene-β-D-ribofuranosyl)-2-(1H)-pyrimidinone 

Downstream Products

• 292045-54-6 1-(2-deoxy-2-methylene-β-D-erythro-pentofuranosyl)-4-N-[γ-[α-[2-(trimethylsilyl)ethoxy]-2-N-[2-(trimethylsilyl)ethoxycarbonyl]folyl]]cytosine 

Relevant articles and documents

Design, Synthesis, and Antineoplastic Activity of 2'-Deoxy-2'-methylidenecytidine

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Synthesis and Anticancer and Antiviral Activities of Various 2'- and 3'-Methylidene-Substituted Nucleoside Analogues and Crystal Structure of 2'-Deoxy-2'-methylidenecytidine Hydrochloride

Various 2'- and 3'-methylidene-substituted nucleoside analogues have been synthesized and evaluated as potential anticancer and/or antiviral agents.Among these compounds, 2'-deoxy-2'-methylidene-5-fluorocytidine (22) and 2'-deoxy-2'-methylidenecytidine (23) not only demonstrated potent anticancer activity in culture against murine L1210 and P388 leukemias, Sarcoma 180, and human CCRF-CEM lymphoblastic leukemia, producing ED50 values of 1.2 and 0.3 μM, 0.6 and 0.4 μM, 1.5 and 1.5 μM, and 0.05 and 0.03 μM, respectively, but also were active in mice against murine L1210 leukemia.Of all the tested drug dosage levels (25, 50, and 75 mg/kg, respectively) compound 23 had no toxic deaths and compound 22 yielded only one toxic death at the highest dosage level.On the contrary, in the same study, 1-β-D-arabinofuranosylcytosine (ara-C) resulted in 2/5, 5/5, and 5/5 toxic deaths, respectively.Both compounds 22 and 23 have shown better anticancer activity than ara-C, yielding higher T/C * 100 values and some long-term survivors ( > 60 days).In addition, compounds 22 and 23 were found to have, respectively, approximately 130 and 40 times lower binding affinity for cytidine/deoxycytidine deaminase derived from human KB cells compared to ara-C, suggesting that the two 2'-methylidene-substituted analogues may be more resistant to deamination.Cytoplasmic deoxycytidine kinase (dCK) was required for compounds 22 and 23 action.Furthermore, compounds 14, 22, 23, and 24 also have antiherpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) activity in cell culture.In addition, the crystal structure of 2'-deoxy-2'-methylidenecytidine hydrochloride (23*HCl) was determined by X-ray crystallography.

2'-alkylidenepyrimidine nucleoside derivatives, process for production thereof, and uses thereof

Disclosed are novel 2'-alkylidenepyrimidine nucleoside derivatives represented by formula [I]: STR1 wherein R1 is an amino gorup or a hydroxy group, R2 is a hydrogen atom, a halogen atom or a lower alkyl group, R3 is a hydrogen atom or a lower alkyl group, and R4 is a hydrogen atom or a phosphate residue, or salts thereof. These novel compounds can be produced from uridine or cytidine derivatives by alkylidenating the 2'-position in the sugar moiety thereof with Wittig's reagent. Furthermore, the compounds have remarkable antiviral activities and therefore can provide novel antiviral agents.