N,N'-Dimethylethylenediamine → (S)-5,5-dimethyl-3-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)phenyl)-4-phenyloxazolidin-2-one

HRID 525339Notes

Reaction equation

HRID 525339 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:11]([CH3:20])([CH3:19])[O:10][C:9]2=[O:21])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[NH:28]1[C:36]2[CH:35]=[CH:34][N:33]=[CH:32][C:31]=2[NH:30][C:29]1=[O:37].CNCCNC>[Cu]I.CO.O.C(O)CCC>[CH3:19][C:11]1([CH3:20])[O:10][C:9](=[O:21])[N:8]([C:5]2[CH:6]=[CH:7][C:2]([N:30]3[C:31]4[CH:32]=[N:33][CH:34]=[CH:35][C:36]=4[NH:28][C:29]3=[O:37])=[CH:3][CH:4]=2)[C@H:12]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:19][C:11]1([CH3:20])[O:10][C:9](=[O:21])[N:8]([C:5]2[CH:6]=[CH:7][C:2]([N:28]3[C:36]4[CH:35]=[CH:34][N:33]=[CH:32][C:31]=4[NH:30][C:29]3=[O:37])=[CH:3][CH:4]=2)[C@H:12]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

9

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 116869163H-Imidazo[4,5-c]pyridin-2-olHCID 89814002(S)-3-(4-bromophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

Product 2

HCID 89815772(S)-5,5-dimethyl-3-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)phenyl)-4-phenyloxazolidin-2-oneYield 4%HCID 89827457(S)-5,5-dimethyl-3-(4-(2-oxo-1H-imidazo[4,5-c]pyridin-3(2H)-yl)phenyl)-4-phenyloxazolidin-2-oneYield 4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 2631-ButanolSolventHCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
110 °C

Procedure

To a vial charged with (S)-3-(4-bromophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.100 mg, 0.289 μmol), potassium carbonate (0.120 mg, 0.867 mol), copper (I) iodide (0.055 mg, 0.289 μmol), and 1H-imidazo[4,5-c]pyridin-2(3H)-one (commercially available from Prime Organics Inc. Woburn, Mass.) (117 mg, 0.867 μmol) were added n-butanol (1.155 μL) and N1,N2-dimethylethane-1,2-diamine (0.051 mg, 0.578 μmol). The suspension was purged with nitrogen, and then sealed and shaken overnight at 110° C. The resulting suspension was cooled to room temperature and filtered through Celite® brand filter aid. The filtrate was dried under reduced pressure and the residue was dissolved in DMSO and purified using RP-HPLC ramping ACN in H2O (10-90%, 0.1% TFA throughout). Separation of isomers was accomplished and the respective product containing eluents were dried under reduced pressure providing products which were lyophilized from MeOH/H2O providing (S)-5,5-dimethyl-3-(4-(2-oxo-1H-imidazo[4,5-c]pyridin-3(2H)-yl)phenyl)-4-phenyloxazolidin-2-one (5 mg, 4%) as a yellow solid and (S)-5,5-dimethyl-3-(4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)phenyl)-4-phenyloxazolidin-2-one (5 mg, 4%) as a light brown solid. Structures were assigned arbitrarily. Data for product A: 1H NMR (500 MHz, DMSO-d6) δ=8.22 (d, J=5.2 Hz, 1H), 8.14 (s, 1H), 7.69-7.64 (m, 2H), 7.51 (d, J=9.0 Hz, 2H), 7.42-7.38 (m, 2H), 7.35-7.28 (m, 3H), 7.12 (d, J=5.2 Hz, 1H), 5.51 (s, 1H), 1.66 (s, 3H), 0.93 (s, 3H). m/z (ESI) 401.2 (M+H)+. Data for product B: 1H NMR (500 MHz, DMSO-d6) δ=8.29 (s, 1H), 8.18 (s, 1H), 7.67 (d, J=9.0 Hz, 2H), 7.47 (d, J=8.9 Hz, 2H), 7.42-7.38 (m, 2H), 7.35-7.28 (m, 3H), 6.99 (d, J=5.4 Hz, 1H), 5.51 (s, 1H), 1.66 (s, 3H), 0.93 (s, 3H). m/z (ESI) 401.2 (M+H)+.

Workup

  1. customThe suspension was purged with nitrogen
  2. customsealed
  3. temperatureThe resulting suspension was cooled to room temperature
  4. filtrationfiltered through Celite® brand
  5. filtrationfilter aid
  6. customThe filtrate was dried under reduced pressure
  7. dissolutionthe residue was dissolved in DMSO
  8. custompurified
  9. customSeparation of isomers
  10. additionthe respective product containing eluents
  11. customwere dried under reduced pressure
  12. customproviding products which

Sources & evidence

ORD record
ord-363e863c3f20499f9124b4d5ae602c55
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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