1-Hydroxybenzotriazole → Diisopropylethylamine

HRID 1484097노트

반응식

HRID 1484097 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

HCID 81531Diisopropylethylamine수율 200%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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)+.

후처리

  1. customreacted for 30 min

출처 및 근거

ORD 기록
ord-c86ea427a9d54fe291e91d02384fcfa8
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09421237B2

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