Pyrrolidine → 1-(4-Methyl-pyridin-3-yl)-3-(2-pyrrolidin-1-yl-pyridin-4-yl)-imidazolidin-2-one

HRID 80112Notes

Reaction equation

HRID 80112 reaction equation
Cl[C:2]1[CH:7]=[C:6]([N:8]2[CH2:12][CH2:11][N:10]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][C:18]=3[CH3:19])[C:9]2=[O:20])[CH:5]=[CH:4][N:3]=1.[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1.C1(C(C2C=CC=CC=2)(P)CC)C=CC=CC=1.CC(C)([O-])C.[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].CO.C1(C)C=CC=CC=1>[CH3:19][C:18]1[CH:17]=[CH:16][N:15]=[CH:14][C:13]=1[N:10]1[CH2:11][CH2:12][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)[CH:7]=2)[C:9]1=[O:20]

Participants

8

Reactant 4

HCID 31268PyrrolidineHCID 21885653Diphenyl phosphinopropaneHCID 23665647Potassium tert-butoxideHCID 49871869Cfg-920

Product 1

HCID 596362441-(4-Methyl-pyridin-3-yl)-3-(2-pyrrolidin-1-yl-pyridin-4-yl)-imidazolidin-2-oneYield 40.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

1-(2-Chloro-pyridin-4-yl)-3-(4-methyl-pyridin-3-yl)-imidazolidin-2-one (58A: 100 mg, 0.3463 mmol) and pyrrolidine (0.145 mL, 1.7317 mmol) were added to toluene previously degassed for 10 minutes. The resulting mixture was stirred for 5 minutes. This was followed by the addition of Pd(OAc)2 (4 mg, 0.01732 mmol), diphenyl-phosphino-propane (14.3 mg, 0.03463 mmol) and potassium tertiary butoxide (66 mg, 0.6926 mmol) and stirring was continued for a further 10 minutes. The reaction mixture was heated to reflux for 16 hours. The reaction was monitored by TLC (10% MeOH in CHC13). The reaction mixture was cooled to room temperature, filtered and the filtrate was concentrated. Purification by column chromatography on silica gel (8% MeOH in chloroform) afforded 45 mg of the product (40% yield).

Workup

  1. custompreviously degassed for 10 minutes
  2. stirringstirring
  3. waitwas continued for a further 10 minutes
  4. temperatureThe reaction mixture was heated
  5. temperatureto reflux for 16 hours
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated
  8. customPurification by column chromatography on silica gel (8% MeOH in chloroform)

Sources & evidence

ORD record
ord-773bde860aed44728c36112ccb5672aa
Source dataset
uspto-grants-2014_09
Patent number
USRE045173E1

Reaction notes

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