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1-Hydroxybenzotriazole → N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycarbonylglycylamino)-D-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-proline 3-Quinolylamide

HRID 2185418
ノート
印刷プレビュー

反応式

HRID 2185418 の反応式
ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:23]([O:27][C:28]([N:30]1[CH2:37][C@@H:36]([NH:38][C:39](=[O:49])[CH2:40][NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:35][C@@H:31]1[C:32](O)=[O:33])=[O:29])([CH3:26])([CH3:25])[CH3:24].[N:50]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH:53]=[C:52]([NH:60][C:61](=[O:80])[C@@H:62]2[CH2:66][C@@H:65]([NH:67][C:68](=[O:79])[C@H:69]([OH:78])[CH2:70][CH2:71][C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=3)[CH2:64][NH:63]2)[CH:51]=1>ClCCl.C(N(CC)CC)C>[N:50]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[CH:53]=[C:52]([NH:60][C:61](=[O:80])[C@@H:62]2[CH2:66][C@@H:65]([NH:67][C:68](=[O:79])[C@H:69]([OH:78])[CH2:70][CH2:71][C:72]3[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=3)[CH2:64][N:63]2[C:32](=[O:33])[C@H:31]2[CH2:35][C@H:36]([NH:38][C:39](=[O:49])[CH2:40][NH:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:37][N:30]2[C:28]([O:27][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:29])[CH:51]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341552n-Tert-butoxycarbonyl-trans-4-(n-tert-butoxycarbonylglycylamino)-d-prolineHCID 59895122trans-4-((R)-2-Hydroxy-4-Phenylbutrylamino)-L-Proline 3-Quinolylamide

生成物 1

HCID 21341554
N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycarbonylglycylamino)-D-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-proline 3-Quinolylamide
収率 65.9%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

Triethylamine (40 μL), 1-hydroxybenzotriazole (36 mg), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (55 mg) were added to a solution of N-tert-butoxycarbonyl-trans-4-(N-tert-butoxycarbonylglycylamino)-D-proline (F, 112 mg) and trans-4-((R)-2-hydroxy-4-phenylbutyrylamino)-L-proline 3-quinolylamide (Compound D101 (H), 100 mg) in dichloromethane (10 mL) at 0° C. The mixture was stirred at room temperature for 18 hr and evaporated in vacuo. The residue was diluted with ethyl acetate and washed with 1 N hydrochloric acid, water, saturated sodium hydrogen carbonate, and brine. The organic layer was dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by silica gel column chromatography (methanol:chloroform=1:50 to 1:20, v/v) to give the title compound (124 mg) as a colorless solid: 1H NMR (400 MHz, CDCl3) δ 1.34-1.44 (m, 18H), 1.86-1.92 (m, 1H), 2.03-2.14 (m, 1H), 2.21-2.64 (m, 3H), 2.71-2.75 (m, 2H), 3.33-3.75 (m, 4H), 3.94-4.10 (m, 2H), 4.21-4.78 (m, 3H), 7.14-7.27 (m, 5H), 7.51-7.71 (m, 2H), 7.83-7.99 (m, 2H), 8.70-8.72 (m, 1H), and 8.96-9.05 (m, 1H).

後処理

  1. customevaporated in vacuo
  2. additionThe residue was diluted with ethyl acetate
  3. washwashed with 1 N hydrochloric acid, water, saturated sodium hydrogen carbonate, and brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customevaporated in vacuo
  6. customThe residue was purified by silica gel column chromatography (methanol

出典と根拠

ORDレコード
ord-693367411205402c90989dd97a4376cd
出典データセット
uspto-grants-2002_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06399629B1

反応ノート

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