Methyl vinyl sulfone → HCID 71730506, compound

HRID 1056218Notes

Reaction equation

HRID 1056218 reaction equation
[CH:1]([S:3]([CH3:6])(=[O:5])=[O:4])=[CH2:2].[NH2:7][CH2:8][C:9]([NH:12][C:13]1[C:14]([CH3:33])=[N:15][C:16]2[C:21]([N:22]=1)=[C:20]([C:23]1[NH:31][C:30]3[CH2:29][CH2:28][NH:27][C:26](=[O:32])[C:25]=3[CH:24]=1)[CH:19]=[CH:18][CH:17]=2)([CH3:11])[CH3:10]>C1COCC1.CC(O)C>[CH3:33][C:14]1[C:13]([NH:12][C:9]([CH3:11])([CH3:10])[CH2:8][NH:7][CH2:2][CH2:1][S:3]([CH3:6])(=[O:5])=[O:4])=[N:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][C:20]=2[C:23]2[NH:31][C:30]3[CH2:29][CH2:28][NH:27][C:26](=[O:32])[C:25]=3[CH:24]=2)[N:15]=1

Participants

5

Reactant 2

HCID 19354Methyl vinyl sulfone2×HCID 71730505HCID 71730505, compound

Product 1

HCID 71730506HCID 71730506, compoundYield 69%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of methyl vinyl sulfone (0.016 mL, 0.178 mmol) (Sigma-Aldrich) in THF (1.0 mL) was added to a mixture of 2-(3-((1-amino-2-methylpropan-2-yl)amino)-2-methylquinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (341) (65 mg, 0.18 mmol) in 2-Propanol (2.00 mL); the reaction mixture was stirred at RT for 16 h when only a small amount of product was observed via lcms. More methyl vinyl sulfone (0.16 mL, 1.78 mmol) was added to the reaction mixture before it was heated in the microwave at 110° C. for 75 min when mostly product was observed via lcms. The crude product was adsorbed onto silica and was purified via automated flash chromatography (silica gel) with 1-6% of 2 M NH3 in MeOH/DCM to give 2-(2-methyl-3-((2-methyl-1-((2-(methylsulfonyl)ethyl)amino)propan-2-yl)amino)quinoxalin-5-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (342, 58 mg, 0.12 mmol, 69% yield) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.63 (s, 6H) 2.57 (s, 3H) 2.91 (s, 2H) 2.92 (s, 3H) 2.97 (t, J=6.94 Hz, 2H) 3.18-3.25 (m, 2H) 3.25-3.31 (m, 2H) 3.65 (td, J=6.85, 2.35 Hz, 2H) 5.52 (br. s., 1H) 5.92 (s, 1H) 7.09 (d, J=1.76 Hz, 1H) 7.36 (t, J=7.82 Hz, 1H) 7.64 (dd, J=8.12, 1.08 Hz, 1H) 7.91 (dd, J=7.63, 0.98 Hz, 1H) 12.49 (br. s., 1H). MS (ESI, pos. ion) m/z: 471.4 (M+1).

Workup

  1. temperaturewas heated in the microwave at 110° C. for 75 min when mostly product
  2. customwas purified

Sources & evidence

ORD record
ord-e03e0fc171274bfc9411477a2537487e
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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