Sodium hydride → 1-({(1R,2R)-2-[1-(2,2-Dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]cyclopropyl}methyl)-3-methylimidazolidine-2,4-dione

HRID 629908Notes

Reaction equation

CS(O[CH2:6][C@@H:7]1[CH2:9][C@H:8]1[C:10]1[N:15]=[C:14]2[N:16]([CH3:25])[C:17](=[O:24])[N:18]([CH2:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:13]2=[CH:12][CH:11]=1)(=O)=O.[CH3:26][N:27]1[C:31](=[O:32])[CH2:30][NH:29][C:28]1=[O:33].[H-].[Na+]>CN(C=O)C>[CH3:22][C:20]([CH3:21])([CH3:23])[CH2:19][N:18]1[C:13]2[C:14](=[N:15][C:10]([C@@H:8]3[CH2:9][C@H:7]3[CH2:6][N:29]3[CH2:30][C:31](=[O:32])[N:27]([CH3:26])[C:28]3=[O:33])=[CH:11][CH:12]=2)[N:16]([CH3:25])[C:17]1=[O:24]

Participants

Conditions

Temperature: 0 °C

Procedure

{(1R,2R)-2-[1-(2,2-Dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]cyclopropyl}methyl methanesulfonate (31-5, 68 mg, 0.18 mmol, 1.0 equiv) was added to anhydrous DMF (0.92 mL) and cooled to 0° C. 3-Methylimidazolidine-2,4-dione (31-6, 105 mg, 0.92 mmol, 5.0 equiv) and NaH (37 mg, 0.92 mmol, 5.0 equiv, 60% dispersion in oil) were added sequentially and the resulting mixture was warmed to RT. After 18 h, LCMS showed complete consumption of 31-5. Purification by reverse-phase HPLC (10-100% 0.1% TFA in H2O:CH3CN) afforded 31-7 as a colorless oil. MS m/z (M+H): calculated=332.1969; observed=332.1971.

Workup

temperaturethe resulting mixture was warmed to RT
customconsumption of 31-5
customPurification by reverse-phase HPLC (10-100% 0.1% TFA in H2O:CH3CN)

Sources & evidence

ORD record: ord-54806d4372ee41c192abfc246d989912
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315518B2

Reaction notes

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