Trifluoroacetic acid → HCID 71730634, compound

HRID 1056226Notes

Reaction equation

HRID 1056226 reaction equation
[C:1]([NH:5][C:6]1[C:7]([CH3:26])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[NH:24][C:23]3[CH2:22][CH2:21][NH:20][C:19](=[O:25])[C:18]=3[CH:17]=1)[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2].[Cl:27]N1C(=O)CCC1=O.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.C(Cl)Cl.CO.CC#N.O>[C:1]([NH:5][C:6]1[C:7]([CH3:26])=[N:8][C:9]2[C:14]([N:15]=1)=[C:13]([C:16]1[NH:24][C:23]3[CH2:22][CH2:21][NH:20][C:19](=[O:25])[C:18]=3[C:17]=1[Cl:27])[CH:12]=[CH:11][CH:10]=2)([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 6422Trifluoroacetic acidHCID 31398ChlorosuccinimideHCID 516892Sodium BicarbonateHCID 71731146HCID 71731146, compound

Product 1

HCID 71730634HCID 71730634, compoundYield 16%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A solution of 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (193) (68 mg, 0.19 mmol) and 1-chloropyrrolidine-2,5-dione (39 mg, 0.29 mmol) in CHCl3 (2 mL) was stirred at RT for 4 h. The reaction mixture was diluted with DCM (100 mL), added to a separatory funnel, and washed with saturated aq. NaHCO3 (2×75 mL) before the organic layer was separated, dried over Na2SO4, and concentrated. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 1-4% of 2 M NH3 in MeOH/DCM to give impure product. The impure product was dissolved in MeOH (˜20 mg/mL) and injected (2×1.0 mL) onto the Shimadzu preparatory LC (Phenomenex Gemini C18, 10 μm, 150×30 mm; 10-100% MeCN/water with 0.1% TFA); the pure fractions were combined, basicified with NaHCO3 (saturated, aq.), extracted with DCM, separated, dried over Na2SO4, and concentrated via rotary evaporation to give 2-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-3-chloro-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (348) (12 mg, 0.03 mmol, 16% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.62 (s, 9H) 2.56 (s, 3H) 2.96 (t, J=6.85 Hz, 2H) 3.63 (td, J=6.85, 2.74 Hz, 2H) 4.87 (s, 1H) 5.66 (br. s., 1H) 7.44 (t, J=7.92 Hz, 1H) 7.72 (dd, J=8.02, 1.37 Hz, 1H) 8.68 (dd, J=7.73, 1.27 Hz, 1H) 12.63 (br. s., 1H). MS (ESI, pos. ion) m/z: 384.0 (M+1).

Workup

  1. additionadded to a separatory funnel
  2. washwashed with saturated aq. NaHCO3 (2×75 mL) before the organic layer
  3. customwas separated
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customwas purified
  7. customto give impure product
  8. extractionextracted with DCM
  9. customseparated
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated via rotary evaporation

Sources & evidence

ORD record
ord-613b65d329bf4c1da872a6e95b854d78
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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