Lithium Chloride → HCID 117738000, compound

HRID 593210Notes

Reaction equation

HRID 593210 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[N:6][CH:7]=1.[Cl-].[Li+].C([Sn](CCCC)(CCCC)[C:24]([O:26][CH2:27][CH3:28])=[CH2:25])CCC>C1(C)C=CC=CC=1.C(OCC)(=O)C.[Pd].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:27]([O:26][C:24]([C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:16])[CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])=[N:6][CH:7]=1)=[CH2:25])[CH3:28]

Participants

8

Reactant 3

HCID 433294Lithium ChlorideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 89437205HCID 89437205, compound

Product 1

HCID 117738000HCID 117738000, compoundYield 37.5%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 4-[(5-bromopyrazin-2-yl)amino]-4-oxo-butanoate (A2, 1.00 g, 3.47 mmol) was dissolved in toluene in a microwave vial and lithium chloride, (0.178 g, 4.17 mmol), palladium triphenylphosphone tetrakis (0.405 g, 0.347 mmol) and tributyl(1-ethoxyvinyl)stannane (1.88 g, 5.21 mmol) were added. The reaction mixture was heated in a sealed vial overnight at 100° C. The mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over Na2SO4, and the solvent were evaporated. The product was purified by flash chromatography (AcOEt/cyclohexane: 1/99→99/1) to give methyl 4-[[5-(1-ethoxyvinyl)pyrazin-2-yl]amino]-4-oxo-butanoate (0.36 g, 1.3 mmol, 37% Yield). This product (0.34 g, 1.2 mmol) was dissolved in tetrahydrofuran (2.20 g, 2.4 mL) and hydrochloric acid (1.2 mL, 2.4 mmol. 2M) was added. After 1 h, brine was added to the mixture and it was extracted 3 times with ethyl acetate. The combined organic layers were dried over MgSO4 and evaporated. The product was purified by flash chromatography (AcOEt/cyclohexane: 1/99→99/1) to give methyl 4-[(5-acetylpyrazin-2-yl)amino]-4-oxo-butanoate A34 (0.14 g, 0.56 mmol, 46% Yield). 1H NMR (400 MHz, CDCl3) 9.52 (1H, s), 9.19 (1H, s), 8.88 (1H, s), 3.70 (3H, s), 2.88-2.75 (2H, m), 2.58 (3H, s).

Workup

  1. additionwere added
  2. washwashed with water
  3. dry with materialThe organic layer was dried over Na2SO4
  4. customthe solvent were evaporated
  5. customThe product was purified by flash chromatography (AcOEt/cyclohexane: 1/99→99/1)

Sources & evidence

ORD record
ord-960ca830f82248cf8d3f0cd0d460bce1
Source dataset
uspto-grants-2016_01
Patent number
US09241489B2

Reaction notes

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