Cesium carbonate → [6-(4-Methoxy-benzylamino)-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1517076Notes

Reaction equation

HRID 1517076 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([N:10]2[CH2:15][CH2:14][CH:13]([N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:12][CH2:11]2)=[O:9])[C:5]([CH3:21])=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1.[CH3:32][O:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH2:39])=[CH:36][CH:35]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:32][O:33][C:34]1[CH:41]=[CH:40][C:37]([CH2:38][NH:39][C:2]2[N:7]=[C:6]([C:8]([N:10]3[CH2:15][CH2:14][CH:13]([N:16]4[CH2:20][CH2:19][CH2:18][CH2:17]4)[CH2:12][CH2:11]3)=[O:9])[C:5]([CH3:21])=[CH:4][C:3]=2[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)=[CH:36][CH:35]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 754524-MethoxybenzylamineHCID 44547211[6-Chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

Product 1

HCID 58016724[6-(4-Methoxy-benzylamino)-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 82%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Procedure

A suspension of 1.25 g (2.8 mmol) of [6-chloro-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 3), 0.069 g (0.1 mmol) of [rac]-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, 0.025 g (0.1 mmol) of palladium(II) acetate and 0.40 g (2.9 mmol) of 4-methoxy-benzylamine in 30 ml of toluene was stirred at RT; 1.08 g (3.3 mmol) of cesium carbonate was added and the reaction mixture subsequently heated up to reflux. After 18 hours, it was cooled down to RT, poured into crashed ice and extracted twice with EtOAc; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1) to give 1.25 g (82%) of the title compound as light yellow solid. MS: 553.3 (MH+).

Workup

  1. temperaturethe reaction mixture subsequently heated up
  2. temperatureto reflux
  3. temperatureit was cooled down to RT
  4. additionpoured
  5. extractionextracted twice with EtOAc
  6. washthe organic phases were washed with water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1)

Sources & evidence

ORD record
ord-84ab71ede630487398bc3f80b74fa28f
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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