Trifluoroacetic acid → HCID 89783666, compound

HRID 1056067Notes

Reaction equation

HRID 1056067 reaction equation
[H-].[Na+].[CH3:3][S:4]([NH2:7])(=[O:6])=[O:5].F[C:9]1[C:10]([CH3:29])=[N:11][C:12]2[C:17]([N:18]=1)=[C:16]([C:19]1[NH:27][C:26]3[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=3[CH:20]=1)[CH:15]=[CH:14][CH:13]=2.[C:30]([OH:36])([C:32]([F:35])([F:34])[F:33])=[O:31]>CN(C=O)C.CS(C)=O>[F:33][C:32]([F:35])([F:34])[C:30]([OH:36])=[O:31].[CH3:29][C:10]1[C:9]([NH:7][S:4]([CH3:3])(=[O:6])=[O:5])=[N:18][C:17]2[C:12]([N:11]=1)=[CH:13][CH:14]=[CH:15][C:16]=2[C:19]1[NH:27][C:26]2[CH2:25][CH2:24][NH:23][C:22](=[O:28])[C:21]=2[CH:20]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 72879MethanesulfonamideHCID 897833202-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783666HCID 89783666, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolvent

Procedure

To a slurry of NaH (60% in mineral oil; 0.064 g, 1.606 mmol) in 1 mL DMF at 0° C. was added methanesulfonamide (TCI America, Portland, Oreg.; 0.153 g, 1.606 mmol) in portions. The ice/water bath was removed and the reaction warmed to RT. 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 126; 0.068 g, 0.229 mmol) was added. After 30 min, the reaction was cooled to 0° C., TFA (0.177 ml, 2.295 mmol) was added (dropwise via syringe), and 1 mL DMSO was added. The solution was filtered through a 0.45 micron syringe filter and purified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-70% ACN/H2O with 0.1% TFA); product-containing fractions were concentrated in vacuo, to give N-(3-methyl-8-(4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridin-2-yl)quinoxalin-2-yl)methanesulfonamide 2,2,2-trifluoroacetate (0.020 g, 0.041 mmol, 18% yield) as a brown solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 12.09 (1H, br. s.), 10.98 (1H, br. s), 8.11 (1H, d, J=7.6 Hz), 7.74 (1H, dt, J=8.0, 0.8 Hz), 7.54-7.66 (1H, m), 7.05-7.15 (1H, m), 7.01 (1H, br. s.), 3.44 (2H, t, J=7.0 Hz), 3.39 (3H, s), 2.91 (2H, t, J=6.9 Hz), 2.68 (3H, s). m/z (ESI, +ve) 372.0 (M+H)+.

Workup

  1. customThe ice/water bath was removed
  2. temperaturethe reaction was cooled to 0° C.
  3. additionwas added
  4. filtrationThe solution was filtered through a 0.45 micron syringe
  5. filtrationfilter
  6. custompurified by rpHPLC (Phenomenex Gemini 150×30 mm C18 column, 10-70% ACN/H2O with 0.1% TFA)
  7. concentrationproduct-containing fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-4825e85fd7214b57a99613b94f7a5dc8
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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