2-Pyrazinecarboxylic acid → 73058-37-4

HRID 1484093Notes

Reaction equation

HRID 1484093 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:14])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH2:6].CN1CCOCC1.[N:22]1[CH:27]=[CH:26][N:25]=[CH:24][C:23]=1[C:28](O)=[O:29].C1(N=C=NC2CCCCC2)CCCCC1.C1C=CC2N(O)N=NC=2C=1>C1COCC1>[CH3:2][O:3][C:4](=[O:14])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[NH:6][C:28]([C:23]1[CH:24]=[N:25][CH:26]=[CH:27][N:22]=1)=[O:29]

Participants

7

Reactant 5

HCID 10472-Pyrazinecarboxylic acidHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 75736Methyl L-phenylalaninate hydrochloride2×HCID 757711-Hydroxybenzotriazole

Product 1

HCID 1258094473058-37-4Yield 98%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

The product L-phenylalanine methyl ester hydrochloride of Preparation example 1 (1.12 g, 5.2 mmol) was dissolved in 20 ml of THF, and neutralized with N-methyl morpholine (NMM) (0.7 ml, 6.2 mmol), then cooled with an ice bath for later use. Pyrazinecarboxylic acid (0.65 g, 5.2 mmol) was added to another reaction flask, dissolved with 20 ml of THF, cooled with an ice water bath, dicyclohexylcarbodiimide (DCC) (1.07 g, 5.2 mmol) and HOBt (0.84 g, 6.2 mmol) were added at 0° C. and reacted for 40 min at 0° C., to which the solution of L-phenylalanine methyl ester hydrochloride in THF prepared, cooled and neutralized according to the above was added, the reaction was monitored by TLC and completed after 2 h, insoluble N,N′-dicyclohexylurea (DCU) was removed by filtration, to the filtrate was added 150 ml of ethyl acetate, washed with 5% sodium bicarbonate solution, 10% citric acid solution, 5% sodium bicarbonate solution, saturated salt solution (2×20 ml) successively. The ethyl acetate layer was dried over anhydrous sodium sulfate, filtered, and evaporated the solvent under reduced pressure, 1.37 g of white solid was obtained with a yield of 98%, m.p.: 152-155° C. 1H-NMR (CDCl3, 300 MHz): δ 3.26 (—CH2, m, 2H), 3.75 (—CH3, s, 3H), 5.09 (—CH, m, 1H), 7.15˜7.32 (-Ph, m, 5H), 8.23 (—CONH, d, 1H), 8.52 (-Pyz, d, 1H), 8.74 (-Pyz, d, 1H), 9.37 (-Pyz, s, 1H).

Workup

  1. temperaturecooled with an ice bath for later use
  2. temperaturecooled with an ice water bath
  3. customprepared
  4. temperaturecooled
  5. additionabove was added
  6. custominsoluble N,N′-dicyclohexylurea (DCU) was removed by filtration, to the filtrate
  7. additionwas added 150 ml of ethyl acetate
  8. washwashed with 5% sodium bicarbonate solution, 10% citric acid solution, 5% sodium bicarbonate solution, saturated salt solution (2×20 ml) successively
  9. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. customevaporated the solvent under reduced pressure

Sources & evidence

ORD record
ord-e4109e86e6ab43549d165683ccb80842
Source dataset
uspto-grants-2016_08
Patent number
US09421237B2

Reaction notes

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