Potassium Carbonate → 1-[2-[4-[5-(2-Methyltetrazol-5-yl)-1-(4-pyridyl)-1H-indol-3-yl]-1,2,3,6-tetrahydro-1-pyridinyl]ethyl]-2-imidazolidinone

HRID 394582Notes

Reaction equation

HRID 394582 reaction equation
Cl.Br[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[CH3:9][N:10]1[N:14]=[N:13][C:12]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[NH:20][CH:19]=[C:18]3[C:24]2[CH2:25][CH2:26][N:27]([CH2:30][CH2:31][N:32]3[CH2:36][CH2:35][NH:34][C:33]3=[O:37])[CH2:28][CH:29]=2)=[N:11]1.C(=O)([O-])[O-].[K+].[K+].CN1CCCC1=O>[Cu].[Cu](I)I.[O-2].[Zn+2].C(OCC)(=O)C>[CH3:9][N:10]1[N:14]=[N:13][C:12]([C:15]2[CH:16]=[C:17]3[C:21](=[CH:22][CH:23]=2)[N:20]([C:3]2[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=2)[CH:19]=[C:18]3[C:24]2[CH2:25][CH2:26][N:27]([CH2:30][CH2:31][N:32]3[CH2:36][CH2:35][NH:34][C:33]3=[O:37])[CH2:28][CH:29]=2)=[N:11]1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 881004-Bromopyridinium chlorideHCID 181772071-[2-[4-[5-(2-methyltetrazol-5-yl)-1H-indol-3-yl]-1,2,3,6-tetrahydropyridin-1-yl]ethyl]-2-imidazolidinone

Product 1

HCID 98692961-[2-[4-[5-(2-Methyltetrazol-5-yl)-1-(4-pyridyl)-1H-indol-3-yl]-1,2,3,6-tetrahydro-1-pyridinyl]ethyl]-2-imidazolidinone

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 83717Copper iodideCatalystHCID 3007857Zinc OxideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

4-Bromopyridine hydrochloride (4×2g) was added during one hour to a mixture of 1-[2-[4-[5-(2-methyltetrazol-5-yl)-1H-indol-3-yl]-1,2,3,6-tetrahydro-1-pyridinyl]ethyl]-2-imidazolidinone (4a) (5 g), potassium carbonate (9 g), copper powder (1 g), copper iodide (0.3 g), zinc oxide (0.3 g) and N-methyl-2-pyrrolidinone (NMP) (75 mL) at 140-150° C. Heating was continued for additional 4 hours. After cooling, ethyl acetate (500 mL) was added. Inorganic salts were filtered off. Water was added and the organic phase was worked up according to the standard procedure above. The remaining crude product was purified by column chromatography on silica gel, eluted with a 50:50:4 mixture of ethyl acetate, ethanol, and triethylamine. Yield 0.7 g of the title compound 5a. mp 177-178° C. 1H NMR (DMSO-d6) δ 2.55-2.65 (m, 4H), 2.75 (t, 2H), 3.20-3.30 (m, 6H) 3.40 (t, 2H), 4.45 (s. 3H), 6.25 (s, 1H), 6.30 (broad t, 1H), 7.75 (dd, 2H, 7.90-8.00 (m, 3H), 8.60 (s, 1H), 8.75 (d, 2H), MS m/z (%): 236 (MH2++), 272 (9%), 245 (17%), 142 (65%), 113 (100%).

Workup

  1. temperatureHeating
  2. temperatureAfter cooling
  3. filtrationInorganic salts were filtered off
  4. additionWater was added
  5. customThe remaining crude product was purified by column chromatography on silica gel
  6. washeluted with a 50:50:4 mixture of ethyl acetate, ethanol, and triethylamine

Sources & evidence

ORD record
ord-1356f84b80b24ebaa26b79fc4594ac3c
Source dataset
uspto-grants-2003_08
Patent number
US06602889B1

Reaction notes

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