Water → 4-{2-(2,4-difluorophenoxy)-5-[(methylsulfonyl)methyl]pyridin-3-yl}-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one

HRID 930939Notes

Reaction equation

HRID 930939 reaction equation
[F:1][C:2]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:3]=1[O:4][C:5]1[C:10]([C:11]2[C:12]3[CH:21]=[CH:20][N:19](S(C4C=CC(C)=CC=4)(=O)=O)[C:13]=3[C:14](=[O:18])[N:15]([CH3:17])[CH:16]=2)=[CH:9][C:8]([CH2:32][S:33]([CH3:36])(=[O:35])=[O:34])=[CH:7][N:6]=1.[OH-].[K+].O>[Br-].C[N+](C)(C)CCCCCCCCCCCCCCCC.O1CCOCC1>[F:1][C:2]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:3]=1[O:4][C:5]1[C:10]([C:11]2[C:12]3[CH:21]=[CH:20][NH:19][C:13]=3[C:14](=[O:18])[N:15]([CH3:17])[CH:16]=2)=[CH:9][C:8]([CH2:32][S:33]([CH3:36])(=[O:34])=[O:35])=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 86721079HCID 86721079, compound

Product 1

HCID 867210804-{2-(2,4-difluorophenoxy)-5-[(methylsulfonyl)methyl]pyridin-3-yl}-6-methyl-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-oneYield 57%

Reagents, catalysts & solvents 2

HCID 5974Hexadecyltrimethylammonium BromideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The product from Example 311f (0.083 g, 0.138 mmol), potassium hydroxide (0.194 g, 3.46 mmol) and N,N,N-trimethylhexadecan-1-aminium bromide (2.52 mg, 6.92 μmol) were combined in dioxane (1.8 mL)/water (0.9 mL) and heated at 100° C. for 4 hours, cooled, and partitioned into ethyl acetate adjusting the pH to 7 with 1 M HCl. The organic layer was washed with saturated aqueous sodium chloride, dried (Na2SO4), filtered, and concentrated. Purification by chromatography (silica gel, 0-4% methanol in dichloromethane) afforded the title compound (0.035 g, 57%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.14 (s, 1H) 8.03 (dd, J=22.74, 2.29 Hz, 2H) 7.30-7.51 (m, 4H) 7.03-7.17 (m, 1H) 6.39 (d, J=2.14 Hz, 1H) 4.57 (s, 2H) 3.60 (s, 3H) 3.00 (s, 3H). MS (ESI+) m/z 446 [M+H]+.

Workup

  1. temperaturecooled
  2. custompartitioned into ethyl acetate adjusting the pH to 7 with 1 M HCl
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by chromatography (silica gel, 0-4% methanol in dichloromethane)

Sources & evidence

ORD record
ord-0bbcc1b6adbd4350a0409bf0268bf728
Source dataset
uspto-grants-2016_03
Patent number
US09296741B2

Reaction notes

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