Cesium carbonate → HCID 58042486, compound

HRID 2048013Notes

Reaction equation

HRID 2048013 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1F)[C:5]([O:7]C)=O.[N:13]1([C:19]2[N:24]=[CH:23][C:22]([OH:25])=[CH:21][N:20]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:32][S:33]([NH2:36])(=[O:35])=[O:34].Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1.CN(C1C=CN=CC=1)C.ClCCl.[Cu]>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:25][C:22]1[CH:23]=[N:24][C:19]([N:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]2)=[N:20][CH:21]=1)[C:5]([NH:36][S:33]([CH3:32])(=[O:35])=[O:34])=[O:7]

Participants

10

Reactant 5

HCID 10796Cesium carbonateHCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 17733354Methyl 3-chloro-4-fluorobenzoateHCID 58042413HCID 58042413, compound

Product 1

HCID 58042486HCID 58042486, compoundYield 10.2%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23978CopperCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 3-chloro-4-fluorobenzoate (23.6 mg, 0.125 mmol) and 2-piperidin-1-ylpyrimidin-5-ol (Preparation 10, 22.4 mg 0.125 mmol) in pyridine (0.5 mL) were added cesium carbonate (122 mg, 0.375 mmol) and copper powder (16 mg, 0.25 mmol) and the reaction mixture was shaken at 120° C. for 16 hours. The reaction mixture was filtered and evaporated in vacuo. Water (1 mL) was added and the mixture extracted with EtOAc (3×1 mL). The combined organic layers were dried over magnesium sulfate, filtered and evaporated in vacuo. The residue was dissolved in tetrahydrofuran (0.7 mL), aqueous lithium hydroxide solution (0.7 mL of a 1M solution, 0.7 mmol) was added and the reaction shaken at 30° C. for 16 hours. The reaction was evaporated in vacuo and a 1 M aqueous solution of hydrochloric acid (0.7 mL) was added. The mixture was extracted three times with EtOAc (3×1 mL), the combined organic layers were dried over magnesium sulfate, filtered and evaporated in vacuo. The resulting residue, methanesulfonamide (11.9 mg, 0.125 mmol), DMAP (45.8 mg, 0.375 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (55 mg, 0.28 mmol) were dissolved in dichloromethane (1 mL) and shaken at 30° C. for 16 hours before evaporation in vacuo. The residue purified on a HPLC column (YMC-pack ODS-AQ 150*30 mm*5 μm, acetonitrile-water (0.1% trifluoroacetic acid) gradient) to afford the title compound (5.23 mg, 12.7 μmol).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customevaporated in vacuo
  3. additionWater (1 mL) was added
  4. extractionthe mixture extracted with EtOAc (3×1 mL)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. dissolutionThe residue was dissolved in tetrahydrofuran (0.7 mL)
  9. additionaqueous lithium hydroxide solution (0.7 mL of a 1M solution, 0.7 mmol) was added
  10. stirringthe reaction shaken at 30° C. for 16 hours
  11. customThe reaction was evaporated in vacuo
  12. additiona 1 M aqueous solution of hydrochloric acid (0.7 mL) was added
  13. extractionThe mixture was extracted three times with EtOAc (3×1 mL)
  14. dry with materialthe combined organic layers were dried over magnesium sulfate
  15. filtrationfiltered
  16. customevaporated in vacuo
  17. stirringshaken at 30° C. for 16 hours before evaporation in vacuo
  18. customThe residue purified on a HPLC column (YMC-pack ODS-AQ 150*30 mm*5 μm, acetonitrile-water (0.1% trifluoroacetic acid) gradient)

Sources & evidence

ORD record
ord-0d9a48291a984064846038e01b79f787
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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