Cesium carbonate → N-(2-(6-(3-Amino-2-oxo-1,2-dihydroquinoxalin-5-yloxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenyl)-1-isobutylpiperidine-2-carboxamide

HRID 1594477Notes

Reaction equation

HRID 1594477 reaction equation
[NH2:1][C:2]1[C:3](=[O:13])[NH:4][C:5]2[C:10]([N:11]=1)=[C:9]([OH:12])[CH:8]=[CH:7][CH:6]=2.Cl[C:15]1[N:20]=[CH:19][N:18]=[C:17]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:22]=2[NH:31][C:32]([CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][N:35]2[CH2:40][CH:41]([CH3:43])[CH3:42])=[O:33])[CH:16]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.C([O-])(O)=O.[Na+]>[NH2:1][C:2]1[C:3](=[O:13])[NH:4][C:5]2[C:10]([N:11]=1)=[C:9]([O:12][C:15]1[N:20]=[CH:19][N:18]=[C:17]([C:21]3[CH:26]=[CH:25][C:24]([C:27]([F:28])([F:29])[F:30])=[CH:23][C:22]=3[NH:31][C:32]([CH:34]3[CH2:39][CH2:38][CH2:37][CH2:36][N:35]3[CH2:40][CH:41]([CH3:43])[CH3:42])=[O:33])[CH:16]=1)[CH:8]=[CH:7][CH:6]=2

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 167483403-amino-5-hydroxyquinoxalin-2(1H)-oneHCID 58691369N-(2-(6-chloropyrimidin-4-yl)-5-(trifluoromethyl)-phenyl)-1-isobutylpiperidine-2-carboxamide

Product 1

HCID 58691431N-(2-(6-(3-Amino-2-oxo-1,2-dihydroquinoxalin-5-yloxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenyl)-1-isobutylpiperidine-2-carboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of 3-amino-5-hydroxyquinoxalin-2(1H)-one (0.067 g, 0.38 mmol, prepared as described in WO04014871), N-(2-(6-chloropyrimidin-4-yl)-5-(trifluoromethyl)-phenyl)-1-isobutylpiperidine-2-carboxamide, Example 39(e), (0.14 g, 0.32 mmol) and Cs2CO3 (0.12 g, 0.38 mmol, Strem) in DMF (2.5 mL) was stirred for 3 d at 25° C. The mixture was diluted with aqueous solution of NaHCO3 (100 mL) and extracted with 1:1 mixture of EtOAc/hexane (2×75 mL). The combined extracts were washed with H2O (2×75 mL) and brine (75 mL), dried over Na2SO4, filtered, and evaporated under reduced pressure. Purification of the residue by silica gel column chromatography (gradient: 25-60% EtOAc/hexane) afforded the title compound as a white solid. MS (ESI, pos. ion.) m/z: 582 (M+1). Mp: >250° C.

Workup

  1. extractionextracted with 1:1 mixture of EtOAc/hexane (2×75 mL)
  2. washThe combined extracts were washed with H2O (2×75 mL) and brine (75 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated under reduced pressure
  6. customPurification of the residue by silica gel column chromatography (gradient: 25-60% EtOAc/hexane)

Sources & evidence

ORD record
ord-2060533b10824d4a970150da8b63a589
Source dataset
uspto-grants-2007_11
Patent number
US07301022B2

Reaction notes

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