Potassium Carbonate → Ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(tert-butylamino)-2-methyl-5-quinoxalinyl)-2-oxoethyl)-4-methyl-3-oxopentanoate

HRID 1056341Notes

Reaction equation

HRID 1056341 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:9]([CH3:15])=[N:10]2)=[O:4].[C:21]([O:25][C:26]([NH:28][C:29]([CH3:39])([CH3:38])[C:30](=[O:37])[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:27])([CH3:24])([CH3:23])[CH3:22].C([O-])([O-])=O.[K+].[K+].C([O-])(O)=O.[Na+]>CN(C=O)C>[C:21]([O:25][C:26]([NH:28][C:29]([CH3:38])([CH3:39])[C:30](=[O:37])[CH:31]([CH2:2][C:3]([C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:16][C:17]([CH3:20])([CH3:19])[CH3:18])[C:9]([CH3:15])=[N:10]2)=[O:4])[C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:27])([CH3:23])([CH3:24])[CH3:22]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 87815948Ethyl 4-((tert-butoxycarbonyl)amino)-4-methyl-3-oxopentanoateHCID 897821422-Bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone

Product 1

HCID 89781969Ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(3-(tert-butylamino)-2-methyl-5-quinoxalinyl)-2-oxoethyl)-4-methyl-3-oxopentanoateYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a sealable vial was added 2-bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606) (1.0 g, 2.97 mmol), ethyl 4-((tert-butoxycarbonyl)amino)-4-methyl-3-oxopentanoate (466a) (0.98 g, 3.57 mmol), DMF (20 mL), and K2CO3 (1.03 g, 7.44 mmol). The solution was stirred at RT for 2 d. The solution was poured into sat NaHCO3 (200 mL) and extracted with EtOAc (3×100 mL). The combined extracts were washed with H2O (3×100 mL), brine (100 mL), dried (Na2SO4) and concentrated onto silica. Purification by silica gel chromatography (0 to 50% EtOAc/hexanes) afforded the title compound as a yellow solid (0.50 g, 0.95 mmol, 32% yield). m/z (ESI, +ve ion) 529.3 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.87 (dd, J=8.0, 1.6 Hz, 1H), 7.68 (dd, J=7.4, 1.6 Hz, 1H), 7.64 (br. s, 1H), 7.35 (t, J=7.7 Hz, 1H), 6.09 (br. s, 1H), 4.61 (dd, J=10.3, 2.8 Hz, 1H), 4.15 (dd, J=18.5, 10.5 Hz, 1H), 3.98-4.08 (m, 2H), 3.46 (dd, J=18.5, 3.4 Hz, 1H), 2.55 (s, 3H), 1.52 (s, 9H), 1.29 (s, 3H), 1.28 (s, 3H), 1.24 (s, 9H), 1.12 (t, J=7.0 Hz, 3H).

Workup

  1. additionThe solution was poured
  2. extractionextracted with EtOAc (3×100 mL)
  3. washThe combined extracts were washed with H2O (3×100 mL), brine (100 mL)
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated onto silica
  6. customPurification by silica gel chromatography (0 to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-38c7b69c2eb744eda26cd685980d595b
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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