Cesium carbonate → Trifluoroacetic acid

HRID 60869Notes

Reaction equation

HRID 60869 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C@H:13]([CH3:17])[C@@H:12]1[CH2:18][NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=1)=[O:10].C([Sn](CCCC)(CCCC)[C:35]1[N:40]=[CH:39][CH:38]=[CH:37][N:36]=1)CCC.[C:49]([O-:52])([O-])=[O:50].[Cs+].[Cs+]>O1CCOCC1>[CH3:17][C@H:13]1[CH2:14][CH2:15][CH2:16][N:11]([C:9]([C:3]2[CH:4]=[C:5]([CH3:8])[CH:6]=[CH:7][C:2]=2[C:35]2[N:40]=[CH:39][CH:38]=[CH:37][N:36]=2)=[O:10])[C@H:12]1[CH2:18][NH:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N:21]=1.[C:49]([OH:52])([C:26]([F:29])([F:28])[F:27])=[O:50]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27632512-(Tributylstannyl)pyrimidineHCID 131737147rac-cis-(2-Bromo-5-methylphenyl)(3-methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidin-1-yl)methanone

Product 2

HCID 6422Trifluoroacetic acidHCID 131737148rac-cis-(3-Methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidin-1-yl)(5-methyl-2-(pyrimidin-2-yl)phenyl)methanone

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

The mixture of rac-cis-(2-bromo-5-methylphenyl)(3-methyl-2-(((5-(trifluoromethyl)pyridin-2-yl)amino)methyl)piperidin-1-yl)methanone (0.03 g, 0.0638 mmol), 2-(tributylstannyl)pyrimidine (0.028 g, 0.0766 mmol), P(PPh3)4 (0.011 g, 0.01 mmol), Cs2CO3 (0.42 g, 0.13 mmol) and dioxane (1 mL) was degassed for 5 min and heated overnight at 140° C. oil bath. The completion of reaction was monitored by analytical HPLC. The mixture was cooled and extracted with EtOAc. The combine organic layers were washed with saturated NaHCO3 and dried over Na2SO4. The solvent was removed in vacuo to obtain the crude, which was purified by preparative-HPLC to obtain the title compound as TFA salt. ESI-MS (m/z): 470, [M+1]+.

Workup

  1. customwas degassed for 5 min
  2. customThe completion of reaction
  3. temperatureThe mixture was cooled
  4. extractionextracted with EtOAc
  5. washThe combine organic layers were washed with saturated NaHCO3
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed in vacuo
  8. customto obtain the crude, which
  9. customwas purified by preparative-HPLC

Sources & evidence

ORD record
ord-3079e6a785c8462d883fb95bda402943
Source dataset
uspto-grants-2016_09
Patent number
US09440982B2

Reaction notes

Loading…