Hydrochloric Acid → HCID 67285910, compound

HRID 1484095Notes

Reaction equation

HRID 1484095 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].Cl.CN1CCOCC1.[N:23]1[CH:28]=[CH:27][N:26]=[CH:25][C:24]=1[C:29]([NH:31][C@H:32]([C:40](O)=[O:41])[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:30].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:40](=[O:41])[C@H:32]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[NH:31][C:29]([C:24]1[CH:25]=[N:26][CH:27]=[CH:28][N:23]=1)=[O:30]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 75736Methyl L-phenylalaninate hydrochloride2×HCID 757711-HydroxybenzotriazoleHCID 15042559N-(Pyrazinylcarbonyl)-L-phenylalanine

Product 1

HCID 67285910HCID 67285910, compoundYield 95.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

L-phenylalanine methyl ester hydrochloride (0.8 g, 3.69 mmol) was dissolved with 20 ml of THF, then the hydrochloric acid was neutralized with NMM (0.49 ml, 4.43 mmol), cooled with an ice bath for later use. N-Pyrazineformyl-L-phenylalanine (1.0 g, 3.69 mmol) of Preparation example 3 was added to another reaction flask, dissolved with 20 ml of THF, and cooled with an ice water bath, dicyclohexylcarbodiimide (DCC) (0.76 g, 3.69 mmol), HOBt (0.60 g, 4.42 mmol) were added at 0° C. and reacted for 40 min at 0° C., then 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 DCU was removed by filtration, to the filtrate was added 80 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, 1.52 g of white solid was obtained with a yield of 95.6%, m.p.: 111˜113° C. 1H-NMR (CDCl3, 300 MHz): δ 3.04 (—CH2, m, 2H), 3.18 (—CH2, d, 2H), 3.69 (—CH3, s, 3H), 4.82 (—CH, m, 2H), 6.36 (—CONH, d, 1H), 6.92˜7.30 (-Ph, m, 10H), 8.26 (—CONH, d, 1H), 8.54 (-Pyz, d, 1H), 8.76 (-Pyz, d, 1H), 9.33 (-Pyz, s, 1H).

Workup

  1. temperaturecooled with an ice bath for later use
  2. additionwas added to another reaction flask
  3. temperaturecooled with an ice water bath
  4. customreacted for 40 min at 0° C.
  5. temperaturecooled
  6. additionabove was added
  7. custominsoluble DCU was removed by filtration, to the filtrate
  8. additionwas added 80 ml of ethyl acetate
  9. washwashed with 5% sodium bicarbonate solution, 10% citric acid solution, 5% sodium bicarbonate solution, saturated salt solution (2×20 ml) successively
  10. dry with materialThe ethyl acetate layer was dried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customevaporated the solvent under reduced pressure

Sources & evidence

ORD record
ord-5d1cba388ee54144a8f59bd5bcb42b49
Source dataset
uspto-grants-2016_08
Patent number
US09421237B2

Reaction notes

Loading…