4-Propylpyrrolidin-2-one → HCID 53629223, compound

HRID 1924319Notes

Reaction equation

HRID 1924319 reaction equation
[CH2:1]([CH:4]1[CH2:8][NH:7][C:6](=[O:9])[CH2:5]1)[CH2:2][CH3:3].Cl[CH2:11][C:12]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[N:15]=[C:14]2[N:22]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=3)[CH:23]=[N:24][C:13]=12>C1COCC1>[CH3:33][O:32][C:29]1[CH:28]=[CH:27][C:26]([CH2:25][N:22]2[C:14]3=[N:15][C:16]([C:18]([F:21])([F:19])[F:20])=[CH:17][C:12]([CH2:11][N:7]4[CH2:8][CH:4]([CH2:1][CH2:2][CH3:3])[CH2:5][C:6]4=[O:9])=[C:13]3[N:24]=[CH:23]2)=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 141781004-Propylpyrrolidin-2-oneHCID 57743065HCID 57743065, compound

Product 1

HCID 53629223HCID 53629223, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-30 °C

Procedure

4-propylpyrrolidin-2-one x1 (0.22 g, 1.1 eq with respect to x199, 1.7 mmol) is dissolved in absolute THF (10 ml). A 1.06 M solution of Li-HMDS in THF (1.76 ml, 1.1 eq, 1.87 mmol) is added at −78° C. in a flow of argon. The reaction mixture is stirred for 15 min at −30° C. and cooled again to −78° C. A solution of 7-(chloromethyl)-3-(4-methoxybenzyl)-5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridine x202 in absolute THF (10 ml) is added dropwise at this temperature. The reaction mixture is allowed to heat up slowly to room temperature. In order to complete the reaction, the reaction mixture is refluxed the next morning for 1 h, and then partitioned between saturated aqueous NH4Cl and ethyl acetate. The organic layer is dried with anhydrous sodium sulfate and evaporated. The product is purified by HPLC (water/acetonitrile) to afford 0.14 g of 1-{[3-(4-methoxybenzyl)-5-(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-7-yl]methyl}-4-propylpyrrolidin-2-one x205 (0.14 g).

Workup

  1. temperaturecooled again to −78° C
  2. temperatureto heat up slowly to room temperature
  3. customthe reaction
  4. temperaturethe reaction mixture is refluxed the next morning for 1 h
  5. custompartitioned between saturated aqueous NH4Cl and ethyl acetate
  6. dry with materialThe organic layer is dried with anhydrous sodium sulfate
  7. customevaporated
  8. customThe product is purified by HPLC (water/acetonitrile)

Sources & evidence

ORD record
ord-a36bba85bb5e4b7cacb3fc1cc012393f
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

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