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1-Hydroxybenzotriazole → N-(N-Acetyl-tyrosinyl-valinyl-(4(R)-allyloxy prolinyl))-3(S)-amino-4-oxobutanoic acid

HRID 502319
ノート
印刷プレビュー

反応式

HRID 502319 の反応式
CO[C:3](=[O:35])[C@@H:4]1[CH2:8][C@@H:7]([O:9][CH2:10][CH:11]=[CH2:12])[CH2:6][N:5]1[C:13](=[O:34])[C@H:14]([CH:31]([CH3:33])[CH3:32])[NH:15][C:16](=[O:30])[C@H:17]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1)[NH:18][C:19](=[O:21])[CH3:20].Cl.CO[C:39](=[O:49])[C@@H:40]1[CH2:44][C@@H:43]([O:45]CC=C)C[NH:41]1.N(C(C)=O)[C@H](C(N[C@H](C(O)=O)C(C)C)=O)CC1C=CC([OH:59])=CC=1.C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>ClCCl.CN(C)C=O.C(OCC)(=O)C>[C:19]([NH:18][C@H:17]([C:16]([NH:15][C@H:14]([C:13]([N:5]1[CH2:6][C@H:7]([O:9][CH2:10][CH:11]=[CH2:12])[CH2:8][C@H:4]1[C:3]([NH:41][C@H:40]([CH:39]=[O:49])[CH2:44][C:43]([OH:59])=[O:45])=[O:35])=[O:34])[CH:31]([CH3:32])[CH3:33])=[O:30])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1)(=[O:21])[CH3:20]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

10

反応物 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 22875497N-Acetyl-tyrosinyl-valineHCID 668534754(R)-Allyloxyproline methyl ester hydrochlorideHCID 67541324N-Acetyl-tyrosinyl-valinyl-(4(R)-allyloxyproline) methyl ester

生成物 1

HCID 59901771N-(N-Acetyl-tyrosinyl-valinyl-(4(R)-allyloxy prolinyl))-3(S)-amino-4-oxobutanoic acid

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

N-Acetyl-tyrosinyl-valinyl-(4(R)-allyloxyproline) methyl ester. 4(R)-Allyloxyproline methyl ester hydrochloride (1.05 g, 4.75 mmol) and N-acetyl-Tyr-Val-OH (1.68 g, 5.21 mmol) were dissolved in 10 ml of a 1:1 mixture of dichloromethane and dimethylformamide and cooled to 0° C. Diisopropylethylamine (1 ml, 5.93 mmol) was added to the cooled mixture followed by the addition of N-hydroxybenzotriazole (0.769 g, 5.69 mmol) and 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.18 g, 6.2 mmol). After stirring for 2 hours, the mixture was warmed to room temperature and stirred for 16 hours. The reaction was poured into 150 ml of ethyl acetate and washed with 50 ml each of water, 10% sodium hydrogen sulfate, and 10% sodium bicarbonate. The organic layer was dried over sodium sulfate, filtered, and evaporated to give a light yellow solid. This was purified by flash chromatography eluting with dichloromethane/methanol/pyridine (100:3:0.5) to give 780 mg of the title compound. 1H NMR (CD3OD) δ 7.02-6.96 (2H, d), 6.67-6.63 (2H, d), 5.95-5.85 (1H, m), 5.34-5.27 (1H, d), 5.16-5.13 (1H, d), 4.53-4.38 (3H, m), 4.28-4.22 (1H, m), 4.12-3.97 (3H, m), 3.82-3.73 (1H, m), 3.72 (3H, s), 3.04-2.88 (2H, m), 2.85-2.72 (2H, m), 2.45-2.34 (1H, m), 2.08-1.95 (2H, m), 1.92 (3H, s), 1.00-0.92 (6H, 2×d).

後処理

  1. temperaturethe mixture was warmed to room temperature
  2. stirringstirred for 16 hours
  3. washwashed with 50 ml each of water, 10% sodium hydrogen sulfate, and 10% sodium bicarbonate
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto give a light yellow solid
  8. customThis was purified by flash chromatography
  9. washeluting with dichloromethane/methanol/pyridine (100:3:0.5)

出典と根拠

ORDレコード
ord-d53a589c30f449cc9fdcb28c6ddcf32e
出典データセット
uspto-grants-2010_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07772366B2

反応ノート

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