Ethanol → 2-((S)-1-aminoethyl)-3-(2-(methylsulfonyl)phenyl)quinoxaline-5-carbonitrile

HRID 75380Notes

Reaction equation

HRID 75380 reaction equation
O.NN.CCO.O=C1C2C(=CC=CC=2)C(=O)[N:9]1[C@H:18]([C:20]1[C:29]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[S:36]([CH3:39])(=[O:38])=[O:37])=[N:28][C:27]2[C:26]([C:40]#[N:41])=[CH:25][CH:24]=[CH:23][C:22]=2[N:21]=1)[CH3:19].C([O-])(O)=O.[Na+]>C(Cl)Cl>[NH2:9][C@H:18]([C:20]1[C:29]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[S:36]([CH3:39])(=[O:38])=[O:37])=[N:28][C:27]2[C:26]([C:40]#[N:41])=[CH:25][CH:24]=[CH:23][C:22]=2[N:21]=1)[CH3:19]

Participants

6

Reactant 4

HCID 702EthanolHCID 24654Hydrazine hydrate (1:1)HCID 516892Sodium BicarbonateHCID 866985172-((S)-1-(1,3-dioxoisoindolin-2-yl)ethyl)-3-(2-(methylsulfonyl)phenyl)quinoxaline-5-carbonitrile

Product 1

HCID 866985182-((S)-1-aminoethyl)-3-(2-(methylsulfonyl)phenyl)quinoxaline-5-carbonitrileYield 93.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 5 L three-necked round-bottomed flask equipped with a nitrogen inlet, overhead stirrer and thermocouple was charged with hydrazine hydrate (381 mL, 783 mmol) and EtOH (3.0 L). To the solution was then added 2-((S)-1-(1,3-dioxoisoindolin-2-yl)ethyl)-3-(2-(methylsulfonyl)phenyl)quinoxaline-5-carbonitrile (378 g, 783 mmol) in one portion and heated to 80° C. The reaction was monitored by LC, and deemed complete once the reaction again reached 80° C. The reaction was cooled to room temp (20-21° C.), when DCM (3.0 L) and satd. NaHCO3 solution (600 mL) were added. After phase separation, the organic layer was washed with brine (2×600 mL), concentrated and dried under vacuum and N2 flow for 24 h to afford the product as a light yellow solid 257.7 g with 94.4% LC purity, (no R enantiomer detected) and 93% yield. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.45-8.54 (m, 2H), 8.18 (dt, J=7.7, 1.5 Hz, 1H), 8.05 (dd, J=8.5, 7.4 Hz, 1H), 7.76-8.00 (m, 3H), 3.83-4.03 (m, 1H), 3.25-3.32 (m, 3H), 1.19-1.39 (m, 3H) Mass Spectrum (ESI) m/z=353.0 (M+1).

Workup

  1. customA 5 L three-necked round-bottomed flask equipped with a nitrogen inlet
  2. customdeemed complete once the reaction again reached 80° C
  3. customAfter phase separation
  4. washthe organic layer was washed with brine (2×600 mL)
  5. concentrationconcentrated
  6. dry with materialdried under vacuum and N2 flow for 24 h

Sources & evidence

ORD record
ord-31214550c4644752960d92b380320ea4
Source dataset
uspto-grants-2014_09
Patent number
US08835432B2

Reaction notes

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