Water → 2,2-Dimethylpropionic acid 1-[3-(6,7-difluoro-2-oxo-3,4-dihydro-2H-quinolin-1-yl)-propyl]piperidin-4-yl-methyl ester

HRID 1191526Notes

Reaction equation

HRID 1191526 reaction equation
Cl[CH2:2][CH2:3][CH2:4][N:5]1[C:14]2[C:9](=[CH:10][C:11]([F:16])=[C:12]([F:15])[CH:13]=2)[CH2:8][CH2:7][C:6]1=[O:17].[NH:18]1[CH2:23][CH2:22][CH:21]([CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20][CH2:19]1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[F:16][C:11]1[CH:10]=[C:9]2[C:14](=[CH:13][C:12]=1[F:15])[N:5]([CH2:4][CH2:3][CH2:2][N:18]1[CH2:23][CH2:22][CH:21]([CH2:24][O:25][C:26](=[O:31])[C:27]([CH3:29])([CH3:28])[CH3:30])[CH2:20][CH2:19]1)[C:6](=[O:17])[CH2:7][CH2:8]2

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 179561691-(3-Chloropropyl)-6,7-difluoro-3,4-dihydro-1H-quinolin-2-oneHCID 689120142,2-Dimethylpropionic acid piperidin-4-ylmethyl ester

Product 1

HCID 689104932,2-Dimethylpropionic acid 1-[3-(6,7-difluoro-2-oxo-3,4-dihydro-2H-quinolin-1-yl)-propyl]piperidin-4-yl-methyl esterYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A 4 ml vial was charged with 1-(3-chloropropyl)-6,7-difluoro-3,4-dihydro-1H-quinolin-2-one (52 mg, 0.20 mmol), 2,2-dimethylpropionic acid piperidin-4-ylmethyl ester (45 mg, 0.21 mmol) (40 mg, 0.20 mmol), and Cs2CO3 (200 mg, 0.60 mmol) in dry DMF (1 ml). The reaction was shaken at 80° C. for 3 days and the reaction was poured into water and extracted with EtOAc. The combined organic phase was washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The oily residue was purified by ion-exchange column chromatography to yield the title product as an oil (26 mg, 62 μmol, 31%). 1H NMR (CDCl3) δ 7.07 (dd, J=1.8, 3.1 Hz, 1H), 6.98-6.91 (m, 1H), 3.94-3.87 (m, 4H), 2.94-2.86 (m, 2H), 2.82 (br t, J=6.8 Hz, 2H), 2.02 (dd, J=5.2, 7.6 Hz, 2H), 2.35 (t, J=6.8 Hz, 2H), 1.94 (dt, J=2.0, 11.6 Hz, 2H), 1.74-1.58 (m, 3H), 1.42-1.28 (m, 2H), 1.91 (s, 9H); 13C NMR (CDCl3) δ178.7, 169.7, 149.3 (dd, J=13, 230 Hz), 145.6 (dd, J=243, 13 Hz), 136.7 (br), 122.7 (br), 116.6 (d, J=18 Hz), 105.3 (d, J=22 Hz), 68.8, 55.8, 53.7, 42.3, 39.1, 35.7, 31.1, 29.1, 25.2, 24.9; HPLC-MS (ammonium acetate) [M+H]+=423.20.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic phase was washed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe oily residue was purified by ion-exchange column chromatography

Sources & evidence

ORD record
ord-055613b7d852468eab34045b3c844a8a
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

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