Hydrochloric Acid → HCID 66793770, compound

HRID 1623505Notes

Reaction equation

HRID 1623505 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH3:17])[C:12](=[O:18])[CH2:11]3)[CH:5]=[N:6][CH:7]=1.C(N(C(C)C)CC)(C)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30].[OH-].[Na+].Cl>ClCCl.O>[CH3:17][N:13]1[C:14]2[C:10](=[CH:9][C:8]([C:4]3[CH:3]=[C:2]([NH:1][S:29]([CH3:28])(=[O:31])=[O:30])[CH:7]=[N:6][CH:5]=3)=[CH:16][CH:15]=2)[CH2:11][C:12]1=[O:18]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 66793931HCID 66793931, compound

Product 1

HCID 66793770HCID 66793770, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

To a solution of 5-(5-amino-pyridin-3-yl)-1-methyl-1,3-dihydro-indol-2-one, prepared as described in Example 3, (35 mg, 0.146 mmol), in dichloromethane (2.0 mL) was added diisopropylethylamine (75 pt, 0.44 mmol). The reaction was cooled to −10° C. and methanesulfonyl chloride (22 μL, 0.28 mmol) was added. After 15 minutes the reaction was quenched with saturated aqueous sodium bicarbonate and diluted with dichloromethane. The layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated. The resulting residue was dissolved in methanol (5 mL) and treated with 2 M aqueous sodium hydroxide (0.5 mL, 1 mmol) and permitted to stir at room temperature for 10 minutes. The reaction was then diluted with dichloromethane and water and the pH of the solution was brought to ca. 7 via the careful addition of 1M aqueous HCl. The layers were separated and the aqueous layer was extracted four additional times with dichloromethane and one time with ethyl acetate. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane, 0 to 7%) to furnish N-[5-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-pyridin-3-yl]-methanesulfonamide; HRMS: (ES+) m/z 318.0912 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 3.11 (s, 3H), 3.28 (s, 3H), 3.62 (s, 2H), 6.94 (d, J=8.1 Hz, 1H), 7.50 (s, 1H), 7.51-7.59 (m, 1H), 7.91 (s, 1H), 8.41 (d, J=2.5 Hz, 1H), 8.67 (d, J=1.8 Hz, 1H).

Workup

  1. customAfter 15 minutes the reaction was quenched with saturated aqueous sodium bicarbonate
  2. additiondiluted with dichloromethane
  3. customThe layers were separated
  4. dry with materialthe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe resulting residue was dissolved in methanol (5 mL)
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted four additional times with dichloromethane and one time with ethyl acetate
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane, 0 to 7%)

Sources & evidence

ORD record
ord-7941bbdc285a4d559bce2d0fd4e41736
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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