Pyridine → HCID 58166405, compound

HRID 1405986Notes

Reaction equation

HRID 1405986 reaction equation
[CH2:1]([S:4][C:5]1[C:10]([F:11])=[CH:9][NH:8][C:7](=[O:12])[N:6]=1)[CH:2]=[CH2:3].[S:13]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14]1.N1C=CC=CC=1.C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=O>C(Cl)Cl.O.CC([O-])=O.CC([O-])=O.[Cu+2]>[CH2:1]([S:4][C:5]1[C:10]([F:11])=[CH:9][N:8]([C:15]2[CH:16]=[CH:17][S:13][CH:14]=2)[C:7](=[O:12])[N:6]=1)[CH:2]=[CH2:3]

Participants

8

Reactant 4

HCID 1049PyridineHCID 6049Ethylenediaminetetraacetic AcidHCID 581760Thiophene-3-boronic acidHCID 178460812HCID 178460812, compound

Product 1

HCID 58166405HCID 58166405, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

This material was prepared by the procedure described in J. Org. Chem. 2006, 71, 9183-9190. To a stirred suspension of dry Cu(OAc)2 (1.02 g, 5.64 mmol), 4-(allylthio)-5-fluoro-pyrimidin-2(1H)-one (700 mg, 3.76 mmol), thiophen-3-ylboronic acid (962 mg, 7.52 mmol), and activated 3 Å molecular sieves (2 g) in dry CH2Cl2 (30 mL) was added pyridine (595 mg, 7.52 mmol) at room temperature. The mixture was stirred for 24 h at ambient temperature in the presence of air. The reaction mixture was diluted with CH2Cl2 (30 mL), filtered through a pad of Celite, and washed with water (50 mL) in the presence of ethylenediaminetetraacetic acid (EDTA; 700 mg, 2.4 mmol). The colorless organic phase was dried over MgSO4 and was concentrated in vacuo. The residue was purified by normal phase chromatography (isocratic, 2:1 petroleum ether:EtOAc) to afford 4-(allylthio)-5-fluoro-1-(thiophen-3-yl)pyrimidin-2(1H)-one (290 mg, 29%) as a yellow solid: mp 125-127° C.; 1H NMR (301 MHz, DMSO-d6) δ 8.52-8.35 (m, 1H), 7.81 (s, 1H), 7.69-7.55 (m, 1H), 7.32 (d, J=3.5 Hz, 1H), 6.05-5.81 (m, 1H), 5.36 (d, J=16.9 Hz, 1H), 5.18 (d, J=9.8 Hz, 1H), 3.89 (d, J=6.4 Hz, 2H); ESIMS m/z 269 ([M+H]+).

Workup

  1. customThis material was prepared by the procedure
  2. filtrationfiltered through a pad of Celite
  3. dry with materialThe colorless organic phase was dried over MgSO4
  4. concentrationwas concentrated in vacuo
  5. customThe residue was purified by normal phase chromatography (isocratic, 2:1 petroleum ether:EtOAc)

Sources & evidence

ORD record
ord-94e2dde417864039807dd242918d31ae
Source dataset
uspto-grants-2014_12
Patent number
US08916579B2

Reaction notes

Loading…