Trifluoroacetic acid → HCID 71731516, compound

HRID 1056206Notes

Reaction equation

HRID 1056206 reaction equation
F[C:2]1[C:3]([CH3:22])=[N:4][C:5]2[C:10]([N:11]=1)=[C:9]([C:12]1[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=1)[CH:8]=[CH:7][CH:6]=2.Cl.[CH3:24][C:25]1([CH2:28][NH2:29])[CH2:27][CH2:26]1.CCN(C(C)C)C(C)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>CS(C)=O.CC#N.O>[CH3:22][C:3]1[C:2]([NH:29][CH2:28][C:25]2([CH3:24])[CH2:27][CH2:26]2)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:12]2[NH:20][C:19]3[CH2:18][CH2:17][NH:16][C:15](=[O:21])[C:14]=3[CH:13]=2)[N:4]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 533992701-(1-Methylcyclopropyl)methanamine--hydrogen chloride (1/1)HCID 897833202-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 71731516HCID 71731516, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A solution of 2-(3-fluoro-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (126) (46 mg, 0.16 mmol), (1-methylcyclopropyl)methanamine hydrochloride (37.8 mg, 0.310 mmol) (Princeton Bio, Princeton, N.J.), and DIEA (136 μL, 0.776 mmol) in DMSO (1.5 mL) was heated at 100° C. for 1.5 h. The crude product was diluted in DMSO (˜20 mg/mL) and injected (3×1.0 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-(2-methyl-3-(((1-methylcyclopropyl)methyl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (335) (5 mg, 0.014 mmol, 9% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 0.25-0.29 (m, 2H) 0.57-0.62 (m, 2H) 1.20 (s, 3H) 2.56 (s, 3H) 2.89 (t, J=6.75 Hz, 2H) 3.45 (td, J=6.75, 2.35 Hz, 2H) 3.57 (d, J=5.87 Hz, 2H) 6.97 (br. s., 1H) 7.14 (d, J=1.96 Hz, 1H) 7.19 (t, J=5.87 Hz, 1H) 7.32 (t, J=7.82 Hz, 1H) 7.57 (dd, J=8.02, 1.17 Hz, 1H) 7.87 (dd, J=7.53, 1.08 Hz, 1H) 12.04 (br. s., 1H). MS (ESI, pos. ion) m/z: 362.1 (M+1).

Workup

  1. extractionextracted with DCM
  2. customseparated
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated via rotary evaporation

Sources & evidence

ORD record
ord-167c673b49a84e9ba86eef944c3fb6e8
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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