1-Hydroxybenzotriazole → Diisopropylethylamine

HRID 1484097Notes

Reaction equation

HRID 1484097 reaction equation
N1C=CN=CC=1C(N[C@H:10]([C:18]([NH:20][C@H:21]([C:29](O)=O)[CH2:22]C1C=CC=CC=1)=O)CC1C=CC=CC=1)=O.[CH:32]1[CH:33]=CC2N(O)N=NC=2[CH:37]=1.Cl.C(N=C=NCCCN(C)C)C>C1COCC1>[CH:32]([N:20]([CH2:18][CH3:10])[CH:21]([CH3:22])[CH3:29])([CH3:33])[CH3:37]

Participants

5

Reactant 3

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67286253(Pyrazine-2-carbonyl)-L-phenylalanyl-L-phenylalanine

Product 1

HCID 81531DiisopropylethylamineYield 200%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-pyrazineformyl-L-phenylalanyl-L-phenylalanine (0.42 g, 1 mmol) of Preparation example 5 was dissolved in 7 ml of THF, HOBt (0.16 g, 1.2 mmol) and 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.29 g, 1.5 mmol) were added at −20° C., then reacted for 30 min followed by addition of LeuBdiol-NH2 (0.3 g, 1 mmol) obtained in Preparation example 42 and N,N-diisopropylethylamine (0.26 g, 2 mmol), the mixture was stirred overnight at −20° C. TLC monitored the reaction, the after the reaction was completed, insoluble substance was removed by filtration, and solvent was evaporated under reduced pressure, the residue was dissolved with 20 ml of ethyl acetate, washed with 10% citric acid solution, 5% sodium bicarbonate solution, saturated table salt solution (3×15 ml) successively. The ethyl acetate layer was dried over anhydrous magnesium sulfate, filtered, concentrated, and the residue was separated by column chromatography to give 0.54 g of compound 4a as a white solid with a yield of 82%. m.p.: 78-80° C.; 1H-NMR (CDCl3, 500 MHz): δ 9.31-9.26 (m, 1H), 8.82-8.77 (m, 1H), 8.58-8.54 (m, 1H), 8.23-8.19 (m, 1H), 7.32-6.99 (m, 10H), 6.48-6.42 (m, 1H), 5.72-5.67 (m, 1H), 4.80-4.77 (m, 1H), 4.59-4.55 (m, 1H), 4.36-4.33 (m, 1H), 3.19-3.09 (m, 4H), 2.90-2.88 (m, 1H), 2.36-2.22 (m, 2H), 2.08-2.03 (m, 1H), 1.94-1.86 (m, 2H), 1.47-1.39 (m, 3H), 1.30-1.28 (m, 3H), 1.29-1.21 (m, 3H), 0.90-0.83 (m, 9H); 13C-NMR (CDCl3, 125 MHz): 169.86, 169.77, 163.21, 147.63, 144.33, 143.52, 142.69, 136.25, 135.94, 129.22, 129.13, 128.81, 128.45, 127.28, 126.72, 84.72, 54.73, 54.27, 51.50, 39.41, 39.37, 38.37, 38.03, 37.84, 37.64, 35.68, 28.53, 28.44, 27.05, 26.36, 26.32, 25.58, 23.96, 22.36; MS (EI): m/z 665.6 (M)+.

Workup

  1. customreacted for 30 min

Sources & evidence

ORD record
ord-c86ea427a9d54fe291e91d02384fcfa8
Source dataset
uspto-grants-2016_08
Patent number
US09421237B2

Reaction notes

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