1-Hydroxybenzotriazole → N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycarbonylaminomethyl)-L-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-Proline 3-Quinolylamide

HRID 2185427ノート

反応式

HRID 2185427 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]([CH2:38][NH:39][C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:35][C@H:31]1[C:32]([OH:34])=O)=[O:29])([CH3:26])([CH3:25])[CH3:24].[N:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:50]=[C:49]([NH:57][C:58](=[O:89])[C@@H:59]2[CH2:63][C@@H:62]([NH:64][C:65](=[O:76])[C@H:66]([OH:75])[CH2:67][CH2:68][C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)[CH2:61][N:60]2C(=O)[C@H]2C[C@H](NC(=O)CN)CN2)[CH:48]=1>ClCCl.C(Cl)(Cl)Cl.C(N(CC)CC)C>[N:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:50]=[C:49]([NH:57][C:58](=[O:89])[C@@H:59]2[CH2:63][C@@H:62]([NH:64][C:65](=[O:76])[C@H:66]([OH:75])[CH2:67][CH2:68][C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=3)[CH2:61][N:60]2[C:32](=[O:34])[C@@H:31]2[CH2:35][C@@H:36]([CH2:38][NH:39][C:40]([O:42][C:43]([CH3:45])([CH3:44])[CH3:46])=[O:41])[CH2:37][N:30]2[C:28]([O:27][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:29])[CH:48]=1

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21341428trans-4-Glycylamino-D-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-proline 3-QuinolylamideHCID 213415491-(1,1-Dimethylethyl) (2S,4S)-4-((((1,1-dimethylethoxy)carbonyl)amino)methyl)-1,2-pyrrolidinedicarboxylate

生成物 1

HCID 21341551N-tert-Butoxycarbonyl-trans-4-(N-tert-Butoxycarbonylaminomethyl)-L-Prolyl-trans-4-((R)-2-Hydroxy-4-Phenylbutyrylamino)-L-Proline 3-Quinolylamide収率 78.9%

試薬・触媒・溶媒 3

HCID 6212Chloroform溶媒HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

Triethylamine (36 μL), 1-hydroxybenzotriazole (9 mg) and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (49 mg) were added to a stirred solution of N-tert-butoxycarbonyl-trans-4-(N-tert-butoxycarbonylamino)methyl-L-Proline (D, 80 mg) and trans-4-((R)-2-hydroxy-4-phenylbutrylamino)-L-proline 3-quinolylamide (CompoundDlol (H), 97 mg) in dichloromethane (4 mL) at 0° C. The mixture was stirred at room temperature overnight. The reaction mixture was diluted with chloroform and washed with 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 (chloroform:methanol=100:1, v/v) to give the title compound (97 mg) as a colorless foam: 1H NMR (400 MHz, CDCl3) δ 1.41 (s, 9H), 1.45 (s, 9H), 1.97-2.31 (m, 6H), 2.71 (m, 1H), 2.74 (m, 2H), 3.21 (m, 2H), 3.64 (m, 2H), 3.79 (m, 1H), 3.91 (m, 1H), 4.49-4.55 (m, 2H), 4.79 (m, 1H), 4.93 (m, 2H), 7.17-7.52 (m, 9H), 8.49 (s, 1H), 8.57 (s, 1H), and 10.2 (m, 1H).

後処理

  1. washwashed with saturated sodium hydrogen carbonate and brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. customevaporated in vacuo
  4. customThe residue was purified by silica gel column chromatography (chloroform

出典と根拠

ORDレコード
ord-3468e205b1424d6892099f289a6a6645
出典データセット
uspto-grants-2002_06
特許番号
US06399629B1

反応ノート

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