Potassium Carbonate → HCID 21865136, compound

HRID 857676Notes

Reaction equation

HRID 857676 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][C:12]3[N:17]=[CH:16][N:15]=[C:14]([C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][C:19]=4[NH2:28])[CH:13]=3)[CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(N(CC)C(C)C)(C)C.[CH3:38][S:39](Cl)(=[O:41])=[O:40].C([O-])(O)=O.[Na+].C([O-])([O-])=O.[K+].[K+]>ClCCCl.O.C(Cl)Cl.CO>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([O:11][C:12]3[N:17]=[CH:16][N:15]=[C:14]([C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:25])([F:27])[F:26])=[CH:20][C:19]=4[NH:28][S:39]([CH3:38])(=[O:41])=[O:40])[CH:13]=3)[CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 10474988HCID 10474988, compound

Product 1

HCID 21865136HCID 21865136, compound

Reagents, catalysts & solvents 4

HCID 111,2-DichloroethaneSolventHCID 887MethanolSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of 2-[6-(quinolin-7-yloxy)-pyrimidin-4-yl]-5-trifluoromethyl-phenylamine, (Example 163), (0.25 g, 0.65 mmol), N,N-diisopropylethylamine (0.57 mL, 3.3 mmol) in 1,2-dichloroethane (6.5 mL) was added methanesulfonyl chloride (0.12 mL, 1.6 mmol, Aldrich). The mixture was stirred at 40° C. for 72 h. After cooling to room temperature, the reaction mixture was treated with satd NaHCO3 and H2O and extracted with EtOAc (2×75 mL). The combined extracts were washed with H2O (75 mL) and brine (75 mL), dried over Na2SO4, filtered, and concentrated onto silica gel. Purification by silica gel chromatography (gradient, 30 to 60% EtOAc/hexanes) afforded a pale yellow solid. To the solid was added MeOH (5 mL), CH2Cl2 (5 mL) and K2CO3 (0.050 g). The reaction mixture was stirred at room temperature for 24 h and then diluted with H2O and extracted with EtOAc (2×75 mL). The combined extracts were washed with H2O (75 mL), brine (75 mL), dried over Na2SO4, filtered, and concentrated onto silica gel. Purification by silica gel chromatography (gradient, 30 to 60% EtOAc/hexanes) afforded the title compound as a white solid. Mp: 203–204° C. MS (ESI, pos. ion) m/z: 461.0 (M+1).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with EtOAc (2×75 mL)
  3. washThe combined extracts were washed with H2O (75 mL) and brine (75 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated onto silica gel
  7. customPurification by silica gel chromatography (gradient, 30 to 60% EtOAc/hexanes)
  8. customafforded a pale yellow solid
  9. stirringThe reaction mixture was stirred at room temperature for 24 h
  10. extractionextracted with EtOAc (2×75 mL)
  11. washThe combined extracts were washed with H2O (75 mL), brine (75 mL)
  12. dry with materialdried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated onto silica gel
  15. customPurification by silica gel chromatography (gradient, 30 to 60% EtOAc/hexanes)

Sources & evidence

ORD record
ord-2066289894834f0ab43bd5c11c6a91c9
Source dataset
uspto-grants-2006_12
Patent number
US07144888B2

Reaction notes

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