Tetrahydrofuran → (2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)(p-tolyl)methanone

HRID 1508711Notes

Reaction equation

HRID 1508711 reaction equation
Cl[C:2]1[C:3]2[CH2:17][CH2:16][CH2:15][C:4]=2[N:5]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([Cl:14])[CH:9]=2)[N:7]=1.[C:18]1(C)[CH:23]=CC([Mg]Br)=[CH:20][CH:19]=1.[CH2:27]1[CH2:31][O:30][CH2:29][CH2:28]1>>[Cl:14][C:10]1[CH:9]=[C:8]([C:6]2[N:7]=[C:2]([C:29]([C:28]3[CH:27]=[CH:31][C:19]([CH3:20])=[CH:18][CH:23]=3)=[O:30])[C:3]3[CH2:17][CH2:16][CH2:15][C:4]=3[N:5]=2)[CH:13]=[CH:12][CH:11]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 218826774-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidineHCID 178418370HCID 178418370, compound

Product 1

HCID 74221428(2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)(p-tolyl)methanoneYield 37%

Procedure

A 25-mL round bottom flask, with stirrer bar, was charged with 4-chloro-2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine (97 mg, 0.38 mol, 1.0 eq.) and THF (5.0 mL). A solution of 4-tolylmagnesium bromide (1.14 mL, 1.0M in THF, 1.14 mmol, 3.0 eq.) was added dropwise over 1 minute at room temperature. After stirring for 2 hrs at room temperature the reaction was heated to reflux for 2.5 hrs. The reaction was cooled to room temperature and was quenched with 2N HCl and diluted with ethyl acetate (50 mL). The organic layer was washed with sat. sodium chloride (3×5 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue (227 mg) was purified by chromatography on silica gel using hexanes/ethyl acetate (10:0 to 8:2) as the eluent, to afford (2-(3-chlorophenyl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)(p-tolyl)methanone (49 mg, 37% yield) as a yellow solid. MW=348.83. 1H NMR (DMSO-d6, 500 MHz) δ 8.31-8.26 (m, 2H), 7.29 (d, J=8.5 Hz, 2H), 7.62-7.53 (m, 2H), 7.41 (d, J=8.0 Hz, 2H), 3.12 (t, J=7.5 Hz, 2H), 3.06 (t, J=7.0 Hz, 2H), 2.43 (s, 3H), 2.06 (quintet, J=7.5 Hz, 2H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2.5 hrs
  3. temperatureThe reaction was cooled to room temperature
  4. customwas quenched with 2N HCl
  5. additiondiluted with ethyl acetate (50 mL)
  6. washThe organic layer was washed with sat. sodium chloride (3×5 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue (227 mg) was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-a15be69f184a48929c855271c7c64871
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

Loading…