Diethylamine → [(1-{(S)-2-[(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-phenyl-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester

HRID 1915974

반응식

HRID 1915974 반응식
[CH3:1][O:2][C:3](=[O:55])[CH2:4][NH:5][C:6](=[O:54])[C@H:7]([NH:11][C:12](=[O:53])[C@H:13]([NH:35]C(OCC1C2C=CC=CC=2C2C1=CC=CC=2)=O)[CH2:14][S:15][C:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH:8](C)[CH3:9].N(CC)CC.[C:61]([NH:78][C@@H:79]([C:87](O)=[O:88])[CH2:80][C:81]1[CH:86]=[CH:85][CH:84]=[CH:83][CH:82]=1)([O:63][CH2:64][CH:65]1[C:77]2[C:72](=[CH:73][CH:74]=[CH:75][CH:76]=2)[C:71]2[C:66]1=[CH:67][CH:68]=[CH:69][CH:70]=2)=[O:62].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C>CC#N.C(Cl)Cl>[CH3:1][O:2][C:3](=[O:55])[CH2:4][NH:5][C:6]([C:7]1([NH:11][C:12](=[O:53])[C@H:13]([NH:35][C:87](=[O:88])[C@H:79]([NH:78][C:61]([O:63][CH2:64][CH:65]2[C:77]3[CH:76]=[CH:75][CH:74]=[CH:73][C:72]=3[C:71]3[C:66]2=[CH:67][CH:68]=[CH:69][CH:70]=3)=[O:62])[CH2:80][C:81]2[CH:82]=[CH:83][CH:84]=[CH:85][CH:86]=2)[CH2:14][S:15][C:16]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:9][CH2:8]1)=[O:54]

참가 물질

8

반응물 5

HCID 8021DiethylamineHCID 81531DiisopropylethylamineHCID 978332(2R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-phenylpropanoic acidHCID 2724699PyBOPHCID 57696983{(R)-2-[(S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-tritylsulfanyl-propionylamino]-3-methyl-butyrylamino}-acetic acid methyl ester

생성물 1

HCID 58256993[(1-{(S)-2-[(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-phenyl-propionylamino]-3-tritylsulfanyl-propionylamino}-cyclopropanecarbonyl)-amino]-acetic acid methyl ester수율 82.9%

시약·촉매·용매 2

HCID 6342Acetonitrile용매2회HCID 6344Dichloromethane용매

실험 절차

To a solution of 1 (300 mg, 0.40 mmol, 1 eq) in MeCN (8 mL) was added Et2NH (0.8 mL, 10% v/v) dropwise at rt under Ar(g). The solution was stirred at rt for 2 h, then the solvent was removed in vacuo. The excess of amine was co-evaporated with MeCN (3×5 mL), then with a 1:5 mixture of CH2Cl2/hexane (10 mL). A white solid was obtained and the flask was dried under high vacuum for 2 h. To a solution of Fmoc-D-Phenylalanine (173 mg, 0.45 mmol, 1.1 eq) in MeCN (7 mL) at 0° C. was added PyBOP (233 mg, 0.45 mmol, 1.1 eq) and 176 μL of N-ethyldiisopropylamine (1.01 mmol, 2.5 eq) under Ar(g). The crude amine, dissolved in CH2Cl2 (6 mL) was added to the mixture dropwise. The reaction mixture was then left to warm to rt overnight. The mixture was then concentrated in vacuo and the residue was further purified by silica gel column chromatography with hexane/EtOAc (1:2→0:1) to yield 2 as a white solid (294 mg, 82%).

후처리

  1. customthe solvent was removed in vacuo
  2. additionwith a 1:5 mixture of CH2Cl2/hexane (10 mL)
  3. customA white solid was obtained
  4. customthe flask was dried under high vacuum for 2 h
  5. additionwas added to the mixture dropwise
  6. waitThe reaction mixture was then left
  7. temperatureto warm to rt overnight
  8. concentrationThe mixture was then concentrated in vacuo
  9. customthe residue was further purified by silica gel column chromatography with hexane/EtOAc (1:2→0:1)

출처 및 근거

ORD 기록
ord-c1226fb5f28140b187729c5fe483ae82
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08614193B2

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