1-Hydroxybenzotriazole → Diisopropylethylamine

HRID 1484097ノート

反応式

HRID 1484097 の反応式
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]

参加物

5

反応物 3

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

生成物 1

HCID 81531Diisopropylethylamine収率 200%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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)+.

後処理

  1. customreacted for 30 min

出典と根拠

ORDレコード
ord-c86ea427a9d54fe291e91d02384fcfa8
出典データセット
uspto-grants-2016_08
特許番号
US09421237B2

反応ノート

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