Potassium Carbonate → HCID 25214958, compound

HRID 2194767Notes

Reaction equation

HRID 2194767 reaction equation
[CH:1]([C:4]1[C:9](=[O:10])[NH:8][C:7](=[O:11])[NH:6][C:5]=1[C:12]([C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([CH3:22])[CH:21]=1)[C:17]#[N:18])=[O:13])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[I-].[Li+].[CH3:31][O:32][C:33](=[O:44])[CH2:34][C:35]1([CH2:38]OS(C)(=O)=O)[CH2:37][CH2:36]1>CN(C=O)C>[CH3:31][O:32][C:33](=[O:44])[CH2:34][C:35]1([CH2:38][N:6]2[C:5]([C:12](=[O:13])[C:14]3[CH:21]=[C:20]([CH3:22])[CH:19]=[C:16]([C:17]#[N:18])[CH:15]=3)=[C:4]([CH:1]([CH3:3])[CH3:2])[C:9](=[O:10])[NH:8][C:7]2=[O:11])[CH2:37][CH2:36]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 66321Lithium iodideHCID 468803773-(5-Isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrileHCID 58203553Methyl 2-(1-[(methanesulfonyloxy)-methyl]cyclopropyl)acetate

Product 1

HCID 25214958HCID 25214958, compoundYield 13.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
75 °C

Procedure

To a mixture of 3-(5-isopropyl-2,6-dioxo-1,2,3,6-tetrahydro-pyrimidine-4-carbonyl)-5-methyl-benzonitrile (962 mg, 4.16 mmol), anhydrous powdered potassium carbonate (574 mg, 4.16 mmol), and lithium iodide (557 mg, 4.16 mmol), was added DMF (18 mL) at room temperature. After stirring for 30 min, crude (1-methanesulfonyloxymethyl-cyclopropyl)-acetic acid methyl ester (962 mg) in DMF (2 mL) was added. The mixture was then heated in an oil bath (70-80° C.) and stirred for ca. 19 hr. After cooling to room temperature, the mixture was evaporated in vacuo. The residue was dissolved in methanol-dichloromethane (5:95) and filtered through a celite pad. The filtrate was evaporated and the residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (1:2)) to give 230 mg (13%) of {1-[6-(3-cyano-5-methyl-benzoyl)-5-isopropyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-cyclopropyl}-acetic acid methyl ester (82) as a white syrup. 1H-NMR (200 MHz, CDCl3) δ 0.36-0.65 (4H, m), 1.12 (3H, d, J=7.0 Hz), 1.23 (3H, d, J=7.0 Hz), 2.17-2.32 (2H, m), 2.44-2.52 (4H, m), 3.58 (1H, d, J=15.2 Hz), 3.69 (3H, s), 3.76 (1H, d, J=15.2 Hz), 7.79 (1H, s), 7.95 (1H, s), 8.06 (1H, s), 9.36 (1H, s); m/z (EI) 423 (M+).

Workup

  1. stirringstirred for ca. 19 hr
  2. temperatureAfter cooling to room temperature
  3. customthe mixture was evaporated in vacuo
  4. dissolutionThe residue was dissolved in methanol-dichloromethane (5:95)
  5. filtrationfiltered through a celite pad
  6. customThe filtrate was evaporated
  7. customthe residue was purified by silica gel column chromatography (eluent, ethyl acetate:hexane (1:2))

Sources & evidence

ORD record
ord-8bbc0f36990b400f8de8ff5c38cdf807
Source dataset
uspto-grants-2012_12
Patent number
US08334295B2

Reaction notes

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