1-Methyl-2-imidazolidinone

off-white to beige crystalline solid

To a solution of l-(2-chloroethyl)-3-methylurea (3 g, 22 mmol) was dissolved in THF (80 mL) and to the resulting solution was added NaH (2.2 g, 55 mmol). The reaction mixture was stirred at room temperature under N2 for 18 hours, quenched with MeOH, filtrated, the filtrate was dried with Na2S04, concentrated in vacuo to provide l-methylimidazolidin-2-one (1.5 g, yield: 68percent). MS (M+H)+: 101.Step 2-Synthesis of 1-methylimidazolidin-2-one 15.3 g (177 mmol) of 2-imidazolidone was dissolved in 200 mL of 1, 4-dioxane in a 500 mL eggplant flask equipped with an argon gas balloon and cooled on ice, 9.30 g (212 mmol (55percent oil suspension) of sodium hydride ) Was added and the mixture was stirred at room temperature for 30 minutes.Under ice cooling, 20.4 mL (328 mmol) of iodomethane was added and the mixture was stirred for 30 minutes and then stirred at room temperature for 5 hours. The precipitated salt was filtered off, the filtrate was concentrated and the residue was purified by silica gel column chromatography (developing solution: chloroform / methanol = 10/1) to obtain 6.4 g of 1-methyl-2-imidazolidone colorless solid (Yield: 36percent).13.0 mL (149 mmol) of N-methylethylenediamine, 9.01 g (150 mmol) of urea and 10 mL of ethylene glycol were added to a 100 mL recovery flask, and the mixture was stirred at 130 ° C. for 8 hours. Ethylene glycol was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (developing solution: chloroform / methanol = 10/1) to obtain 10.6 g of colorless solid 1-methyl-2-imidazolidone : 71.1percent)A mixture of 1, 2-ethylenediamine (3.0 g, 0.05 mol), dimethyl carbonate (5.4 g, 0.06 mol), sulfamic acid (1.0 g, 0.01 mol) and 4.5 ml of methanol in an autoclave (100 ml, fitted witha thermocouple to measure the temperature and a magnetic stirrer, at 20–60 bar)19 washeated to and kept at 50oC for 3 h (CAUTION). The internal temperature was then raisedto 160oC and maintained at that temperature for 15 h. After that time, heating was stoppedand the system was allowed to cool to room temperature. The low boiling point substanceswere distilled off under vacuum (7.5 mm Hg). Then, acetone (15 ml) was added to the solidresidue and the suspension was stirred for 10 minutes at room temperature. The suspensionwas filtered to remove insoluble material and the filtrate was distilled off under vacuum(7.5 mm Hg) to give 3.0 g (70percent) 2-imidazolidinone as a white solid, mp. 130–132C, lit.20mp. 130–131oC. 1H NMR (400 MHz, CDCl3): δ 3.53 (s, 4H, CH2), 5.37 (s, 2H, NH); 13CNMR (100MHz, CDCl3): δ 40.94, 165.35.13.0 mL (149 mmol) of N-methylethylenediamine, 9.01 g (150 mmol) of urea and 10 mL of ethylene glycol were added to a 100 mL recovery flask, and the mixture was stirred at 130 C. for 8 hours. Ethylene glycol was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (developing solution: chloroform / methanol = 10/1) to obtain 10.6 g of colorless solid 1-methyl-2-imidazolidone : 71.1%)Among the compounds of formula (II), mention may be made especially of the following preferred compounds: parabanic acid ... 4-chlorouracil 5-chlorouracil 5, 6-dihydrouracil 5, 6-dihydro-5-methyluracil 1-methyl-2-imidazolidinone 1, 3-dimethyl-2-imidazolidinone 4, 5-dihydroxyimidazolidin-2-one 1-(2-hydroxyethyl)-2-imidazolidinone ...Among the compounds of formula (II) mention made be made especially of the following particularly preferred compounds: 1, 2-dihdryo-3-H-1, 2, 4-traizol-2-one uracil 1-methyl-2-imidazolidinone 1, 3-dimethyl-2-imidazolidinone 4, 5-dihydroxyimidazolidin-2-one 1-(2-hydroxyethyl)-2-imidazolidinone 4, 5-dihydroxy-1, 3-dimethylimidazolidin-2-one 1, 3-bis(2-hydroxyethyl)-2-imidazolidinone 2-imidazolidone-4-carboxylic acid 1-(2-aminoethyl)-2-imidazole ...Sodium hydrogen (909.07 mg, 22.73 mmol, 60% purity) was dissolved in anhydrous THF (5 mL), the reaction was placed in an ice bath, replaced with nitrogen for 3 times, 2-bromo-6-fluoropyridine (2 g, 11.36 mmol), and 1-methylimidazolidinone (2.28 g, 22.73 mmol) were added at 0C, the mixture was stirred at 70C for 16 hours. Water (20 mL) was added to quench the reaction, then extracted with EA (3×20 mL), the organic phase was washed by saturated brine (20 mL), dried over anhydrous sodium sulfate, the filtrate was concentrated to give the crude product, the crude product was purified by column to give the 56-1. 1H NMR (400MHz, CDCl3) delta = 8.23 (d, J=8.5 Hz, 1H), 7.43 (t, J=7.7 Hz, 1H), 7.05 (d, J=7.5 Hz, 1H), 4.10 - 3.93 (m, 2H), 3.53 - 3.40 (m, 2H), 2.95 - 2.85 (m, 3H), MS m/z:256.10 [M+H]+1. A mixture of Intermediate 5 (100 mg, 0.22 mmol), l-methylimidazolidin-2-one (66 mg, 0.66 mmol), (Pd2(dba)3) (100 mg, 0.11 mmol), t-BuOK (74 mg, 0.66 mmol) and SPhos (44 mg, 0.11 mmol) in dioxane (10 mL) was stirred under nitrogen atmosphere at 100 C for 16 h. The solvent was removed under reduce pressure and the residue was purified by prep-HPLC to give Example 26 (50 mg, 48.1 % yield) as a yellow solid. MS (ESI): mass calcd. for d liieNeO 470.59, m/z found 470.8 [M+H]+. 'H NMR (400 MHz, DMSO-d6) delta ppm 8 45 (d, J = 2.4 Hz, 1H), 7 76 (d, J = 8 4 Hz, 2H), 7.72 (s, 1H), 7.47 (dd, J = 8.4, 2.0 Hz, 1H), 7.38 - 7.31 (m, 3H), 7.10 (d, J = 8.4 Hz, 1H), 7.01 (s, 1H), 6.52 (s, 1H), 4.51 (s, 2H), 4.03 (s, 2H), 3.74 (t, J = 7.2 Hz, 2H), 3.63 (t, J = 5.6 Hz, 2H), 3 41 (t, J = 8.4 Hz, 2H), 2.83 (t, J = 6 0 Hz, 2H), 2.75 (s, 3H).

1-Methyl-2-imidazolidinone is an imidazole derivative used in the preparation of chelated carbene complexes as well as in bioactive compounds such as potent HIV integrase inhibitors active against raltegravir-resistant viruses.

Molecular Weight:100.12
XLogP3:-0.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:100.063662883
Monoisotopic Mass:100.063662883
Topological Polar Surface Area:32.3
Heavy Atom Count:7
Complexity:91.7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes