Water → HCID 46202392, compound

HRID 1845934Notes

Reaction equation

HRID 1845934 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[NH:15][C:14](=[O:19])[CH2:13][CH2:12]2.[CH3:20][O:21][C:22]1[CH:32]=[CH:31][CH:30]=[CH:29][C:23]=1[O:24][CH2:25][CH:26]1[CH2:28][O:27]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]([CH2:28][CH:26]([OH:27])[CH2:25][O:24][C:23]1[CH:29]=[CH:30][CH:31]=[CH:32][C:22]=1[O:21][CH3:20])[C:14](=[O:19])[CH2:13][CH2:12]2

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 98357((o-Methoxyphenoxy)methyl)oxiraneHCID 46202714HCID 46202714, compound

Product 1

HCID 46202392HCID 46202392, compoundYield 49.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(2,4-difluorophenyl)-3,4-dihydroquinolin-2(1H)-one (180 mg, 0.69 mmol) (PT-012, made as in Example 1B, above) and 2-((2-methoxyphenoxy)methyl)oxirane (162 mg, 0.90 mmol) in anhydrous N,N-dimethylformamide (2 ml) was added caesium carbonate (326 mg, 1.00 mmol) in a 5 ml Personal Chemistry microwave reaction vial. The reaction vial was sealed, and subjected to microwave irradiation at 180° C. for 40 minutes. The reaction was cooled, poured into water (10 mL), extracted with ethyl acetate (2×30 mL), and the combined organic phases washed with water (30 mL), 2N sodium carbonate (30 mL), brine (40 mL), dried over sodium sulfate, and the solvent removed under reduced pressure. The residue was subjected to reverse phase HPLC with a gradient of acetonitrile/water (2% to 98%) to afford 6-(2,4-difluorophenyl)-1-(2-hydroxy-3-(2-methoxyphenoxy)propyl)-3,4-dihydroquinolin-2(1H)-one (148 mg, 0.34 mmol, 49%) (compound No. 88)). LCMS mz 440.0 (M+H), 462.0 (M+Na), anal HPLC >95% in purity. 1H NMR (400 MHz; CDCl3) δ 7.46 (d, J=8.6 Hz, 1H); 7.36 (m, 2H); 7.31 (bs, 1H); 6.88-7.03 (m, 6H); 4.36 (m, H); 4.27 (s, 1H), 4.26 (d, J=2.3 Hz, 1H); 4.15 (dd, J=9.8 and 5.5 Hz, 1H); 4.00-4.10 (m, 2H); 3.88 (s, 3H), 2.99 (m, 2H); 2.76 (m, 2H).

Workup

  1. customin a 5 ml Personal Chemistry microwave reaction vial
  2. customThe reaction
  3. customvial was sealed
  4. customirradiation at 180° C. for 40 minutes
  5. temperatureThe reaction was cooled
  6. extractionextracted with ethyl acetate (2×30 mL)
  7. washthe combined organic phases washed with water (30 mL), 2N sodium carbonate (30 mL), brine (40 mL)
  8. dry with materialdried over sodium sulfate
  9. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-e4db49f1454a46d38fa5892d71723c68
Source dataset
uspto-grants-2015_02
Patent number
US08952007B2

Reaction notes

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