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

HRID 1915974

反応式

HRID 1915974 の反応式
[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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒2 回HCID 6344Dichloromethane溶媒

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-c1226fb5f28140b187729c5fe483ae82
出典データセット
uspto-grants-2013_12
特許番号
US08614193B2

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