2-O-Methylcytosine

ChEBI: Pyrimidine substituted with a methoxy group at position C-2 and an amine group at C-4.

Solid

2-O-methylcytosine is pyrimidine substituted with a methoxy group at position C-2 and an amine group at C-4. It has a role as a metabolite. It is an aminopyrimidine, an aromatic ether and a methylcytosine. It derives from a cytosine.

Pre Step A Pre Step A Sodium isopropoxide (61.6 g, 0.75 mol) was mixed with 270 mL of isopropanol Into the reactor and stir well;Followed by input 3-hydroxyacrylonitrile sodium salt(27.3 g, 0.3 mol) and O-Methylisourea monomethyl sulfate (67.0 g, 0.36 mol);70 C and cyclization reaction for 8 hours to obtain a cyclization reaction solution; at atmospheric pressure to evaporate isopropyl alcohol, To give the intermediate; and further adding 100 mL of concentrated hydrochloric acid to the intermediate, raising the temperature to 100 C Incubate for 1 hour; heat and then add 60mL of water to the solution for hot filtration, the resulting filtrate cooled to room temperature; The filtrate was added with 10mol / L sodium hydroxide solution to adjust the pH value. When the pH was 7 ~ 7.5, it was cooled to 10 70 C. After cooling, the mixture was filtered, washed and dried to obtain cytosine 30.4g, The yield was 91.2% and the HPLC content was 99.2%. (56.1 mg, 0.448 mmol). MS (ES+) m/z 419.0 (MH+). 1H NMR (400 MHz, METHANOL-d4) delta ppm 1.03-1.21 (m, 2H) 1.37-1.67 (m, 5H) 1.71-2.00 (m, 4H) 3.04-3.18 (m, 1H) 3.27-3.39 (m, 1H) 3.55 (dd, J=14.15, 4.55 Hz, 1H) 3.74-3.87 (m, 1H) 3.90-4.05 (m, 4H) 4.98 (dd, J=12.13, 5.81 Hz, 1H) 7.10 (s, 1H) 7.74 (d, J=5.56 Hz, 1H) 7.89 (s, 0.7H) 8.21 (s, 0.3H) 8.38 (d, J=5.56 Hz, 1H)4-Bromo-7-fluoro-1H-indole-2-carboxylic acid ethyl ester (170 mg, 0.59 mmol), Pd2 (dba) 3 (54 mg, 0.06 mmol), X-phos (57 mg, 0.12 mmol), Cs2CO3 ( 583mg, 1.78mmol), Under Ar(g), to a mixture of 2-chloropyrazine (1) (252mg, 2.2mmol), 4- Amino-2-methoxypyrimidine (2) (250mg, 2.0mmol), Cs2C03 (1.3g, 4.0mmol) was added degassed dry 1 , 4-dioxane (13mL). The reaction mixture was then flushed with Ar(g) for 1 min before Pd2(dba)3 (92mg, 0.1 mmol) and Xantphos (127mg, 0.22mmol) were added. The reaction mixture was heated up to 90C for 40h. It was then cooled down to rt. EtOAc (15ml_), H20 (10mL) and brine (5ml_) were added to the reaction mixture. The organic phase was separated and the aqueous phase was extracted with EtOAc (15ml_). The organic layers were combined and Pd-scavenger (MP-TMT, ~400mg, 1.3mmol/g) was added. This was shaken for several hours followed by filtration. The filtrate was concentrated in vacuo, dissolved in DMSO (4ml_) and purified by basic prep LCMS to yield (3) as a solid (45mg, 1 1 %).

Molecular Weight:125.13
XLogP3:0.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:125.058911855
Monoisotopic Mass:125.058911855
Topological Polar Surface Area:61
Heavy Atom Count:9
Complexity:88.3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes