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Dicyclohexylcarbodiimide → N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester

HRID 393053
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HRID 393053 반응식
CC(C)(O[C:5]([NH:7][C@H:8]([C:28]([O:30][CH3:31])=[O:29])[CH2:9][NH:10][C:11]([O:13][CH2:14][CH:15]1[C:27]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])=[O:6])C.C1C2C(COC(NC[C@@H](C(OC)=O)N)=O)C3C(=CC=CC=3)C=2C=CC=1.F[C:59](F)(F)[C:60]([OH:62])=O.ClCCl.[Cl:68][C:69]1[CH:77]=[C:76]([C:78]([NH:80][CH2:81][C:82]2[CH:87]=CC=[C:84](O)[CH:83]=2)=[O:79])[CH:75]=[CH:74][C:70]=1C(O)=O.C1C=NC2N(O)N=NC=2C=1.C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C=O.O>[Cl:68][C:69]1[CH:77]=[C:76]([C:78]([NH:80][CH2:81][C:82]2[CH:83]=[CH:84][CH:59]=[C:60]([OH:62])[CH:87]=2)=[O:79])[CH:75]=[CH:74][C:70]=1[C:5]([NH:7][C@H:8]([C:28]([O:30][CH3:31])=[O:29])[CH2:9][NH:10][C:11]([O:13][CH2:14][CH:15]1[C:27]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[C:21]2[C:16]1=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])=[O:6]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 6

HCID 10868DicyclohexylcarbodiimideHCID 181649HOAtHCID 21863450Trifluoroacetic acid methylene chlorideHCID 226613972-Chloro-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acidHCID 59977282(S)-2-tert-butoxycarbonylamino-3-(9H-fluoren-9-ylmethoxycarbonylamino)propionic acid methyl esterHCID 69512100
3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester

생성물 1

HCID 131723024N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester수율 62%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

A solution of N-[(1,1-dimethylethoxy)carbonyl]-3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester (Example 62; 1.50 g, 3.4 mmol) was converted to crude 3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester (1.30 g, 112% of the theoretical amount) by treatment with trifluoroacetic acid/dichloromethane (1:1). A portion of this material (0.50 g) was combined with 2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoic acid (449 mg, 1.5 mmol), HOAT (219 mg, 1.6 mmol) and dicyclohexylcarbodiimide (363 mg, 1.8 mmol) in N,N-dimethylformamide (5 mL) and the reaction mixture was stirred at room temperature over the weekend. Water was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with water and brine, dried, filtered, evaporated, and chromatographed (2-10% methanol/dichloromethane) to give N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(9H-fluoren-9-ylmethoxy)carbonyl]amino-L-alanine, methyl ester (0.57 g, 62%) as a white solid.

후처리

  1. extractionthe mixture was extracted three times with ethyl acetate
  2. washThe combined organic layers were washed with water and brine
  3. customdried
  4. filtrationfiltered
  5. customevaporated
  6. customchromatographed (2-10% methanol/dichloromethane)

출처 및 근거

ORD 기록
ord-0ebe6c892df248b5ac7fc53c286791a3
출처 데이터셋
uspto-grants-2004_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06803384B2

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