Cesium carbonate → 2-benzyl-5-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)pyrimidin-4(3H)-one

HRID 1676299Notes

Reaction equation

HRID 1676299 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([I:11])[S:10][C:3]=12.[CH2:12]([C:19]1[NH:24][C:23](=[O:25])[C:22]([C:26]2[CH:31]=[CH:30][C:29]([OH:32])=[C:28]([F:33])[CH:27]=2)=[CH:21][N:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH2:12]([C:19]1[NH:24][C:23](=[O:25])[C:22]([C:26]2[CH:31]=[CH:30][C:29]([O:32][C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[CH:8]=[C:9]([I:11])[S:10][C:3]=34)=[C:28]([F:33])[CH:27]=2)=[CH:21][N:20]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 177504007-Chloro-2-iodothieno(3,2-b)pyridineHCID 673484592-benzyl-5-(3-fluoro-4-hydroxyphenyl)pyrimidin-4(3H)-one

Product 1

HCID 673469802-benzyl-5-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)pyrimidin-4(3H)-oneYield 17%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a mixture of 7-chloro-2-iodothieno[3,2-b]pyridine (0.030 g, 0.10 mmol; prepared according to the procedure described by Ragan, J. A. Org. Proc. Res. Dev. 2003, 7, 676) and 2-benzyl-5-(3-fluoro-4-hydroxyphenyl)pyrimidin-4(3H)-one (0.025 g, 0.084 mmol) in DMF (1 mL) was added Cs2CO3 (0.033 g, 0.10 mmol). The reaction mixture was stirred at 130° C. for 18 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous NaCl. The phases were separated, and the aqueous phase was re-extracted with EtOAc (2×). The combined organic layers were dried (Na2SO4), filtered and concentrated to yield a crude dark yellow solid. Purification of the crude product was achieved by flash column chromatography (25:1 dichloromethane/methanol) and then by trituration with dichloromethane. The resulting solid was filtered, washed with dichloromethane, collected and dried under vacuum to yield the desired product (0.008 g, 17%) as a pale yellow solid. LRMS (ESI pos) m/e 556 (M+1).

Workup

  1. customprepared
  2. customThe reaction mixture was partitioned between EtOAc and saturated aqueous NaCl
  3. customThe phases were separated
  4. extractionthe aqueous phase was re-extracted with EtOAc (2×)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto yield a crude dark yellow solid
  9. customPurification of the crude product
  10. filtrationThe resulting solid was filtered
  11. washwashed with dichloromethane
  12. customcollected
  13. customdried under vacuum

Sources & evidence

ORD record
ord-662c90a44d2d418d86fca9f07addce20
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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