Cesium carbonate → 2-{2-Chloro-5-[4-(pyrrolidine-1-carbonyl)-piperidin-1-yl]-phenyl}-5-methoxy-benzoimidazole-1-carboxylic acid tert-butyl ester

HRID 77095Notes

Reaction equation

HRID 77095 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=2[N:10]=[C:9]1[C:19]1[CH:24]=[C:23](Br)[CH:22]=[CH:21][C:20]=1[Cl:26])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:27]1[CH2:32][CH2:31][CH:30]([C:33]([N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[O:34])[CH2:29][CH2:28]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:12]2[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=2[N:10]=[C:9]1[C:19]1[CH:24]=[C:23]([N:27]2[CH2:28][CH2:29][CH:30]([C:33]([N:35]3[CH2:39][CH2:38][CH2:37][CH2:36]3)=[O:34])[CH2:31][CH2:32]2)[CH:22]=[CH:21][C:20]=1[Cl:26])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 1520212piperidin-4-yl(pyrrolidin-1-yl)methanoneHCID 66977713HCID 66977713, compound

Product 1

HCID 669777312-{2-Chloro-5-[4-(pyrrolidine-1-carbonyl)-piperidin-1-yl]-phenyl}-5-methoxy-benzoimidazole-1-carboxylic acid tert-butyl esterYield 82%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
80 °C

Procedure

Method F—Step a 2-(5-Bromo-2-chloro-phenyl)-5-methoxy-benzoimidazole-1-carboxylic acid tert-butyl ester (obtained as described in general method 4, step c) (0.10 g, 0.23 mmol), piperidin-4-yl-pyrrolidin-1-yl-methanone (0.05 g, 0.30 mmol) and cesium carbonate (0.37 g, 1.14 mmol) were placed into a dried vial and 3 cycles of vacuum/nitrogen were performed, then dry toluene (0.20 mL) was added. At the same time palladium acetate (0.01 g, 0.05 mmol), and BINAP (0.04 g, 0.07 mmol) were placed into a dried 4 mL vial under nitrogen and 3 cycles of vacuum/nitrogen were performed. Then dry toluene (0.40 mL) was added, at room temperature under nitrogen, and the mixture was added to the first vial. The reaction mixture was heated at 80° C. overnight, cooled to room temperature, EtOAC (3 mL) was added and the mixture filtered off. Solvent was removed and the crude recovered with EtOAc (3.5 mL) and filtered through a 2 g silica column (eluent EtOAc) to afford 0.10 g of the title compound (82%) without further purifications.

Workup

  1. additionthe mixture was added to the first vial
  2. temperaturecooled to room temperature
  3. additionEtOAC (3 mL) was added
  4. filtrationthe mixture filtered off
  5. customSolvent was removed
  6. customthe crude recovered with EtOAc (3.5 mL)
  7. filtrationfiltered through a 2 g silica column (eluent EtOAc)

Sources & evidence

ORD record
ord-0ad1aa1b51db4b0081b8b742278e585a
Source dataset
uspto-grants-2014_09
Patent number
US08835648B2

Reaction notes

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