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

HRID 2185427노트

반응식

HRID 2185427 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 6212Chloroform용매HCID 6344Dichloromethane용매HCID 8471Triethylamine용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-3468e205b1424d6892099f289a6a6645
출처 데이터셋
uspto-grants-2002_06
특허 번호
US06399629B1

반응 노트

불러오는 중…