Diethylamine → 9H-fluoren-9-ylmethyl N-ethylcarbamate;methyl 2-[[1-[[(2S)-2-formamido-3-tritylsulfanylpropanoyl]amino]cyclopropanecarbonyl]amino]acetate

HRID 1915972

반응식

HRID 1915972 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:36]([O:38][CH2:39][CH:40]1[C:52]2[CH:51]=[CH:50][CH:49]=[CH:48][C:47]=2[C:46]2[C:41]1=[CH:42][CH:43]=[CH:44][CH:45]=2)=[O:37])[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]([CH3:10])C.C(NCC)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.N(C(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O)CC(O)=O.C(N(C(C)C)CC)(C)C>CC#N.C(Cl)Cl.C(Cl)Cl.CC#N>[CH:42]1[C:41]2[CH:40]([CH2:39][O:38][C:36](=[O:37])[NH:35][CH2:13][CH3:12])[C:52]3[C:47](=[CH:48][CH:49]=[CH:50][CH:51]=3)[C:46]=2[CH:45]=[CH:44][CH:43]=1.[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][CH:36]=[O:38])[CH2:14][S:15][C:16]([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)[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:8][CH2:10]1)=[O:54]

참가 물질

9

반응물 5

HCID 8021DiethylamineHCID 81531DiisopropylethylamineHCID 93124Fmoc-Gly-OHHCID 2724699PyBOPHCID 57696983{(R)-2-[(S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-tritylsulfanyl-propionylamino]-3-methyl-butyrylamino}-acetic acid methyl ester

생성물 1

HCID 866534029H-fluoren-9-ylmethyl N-ethylcarbamate;methyl 2-[[1-[[(2S)-2-formamido-3-tritylsulfanylpropanoyl]amino]cyclopropanecarbonyl]amino]acetate수율 137.6%

시약·촉매·용매 3

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 21877088Acetonitrile methylene chloride용매

실험 절차

To a solution of 1 (310.5 mg, 0.420 mmol) in MeCN/CH2Cl2 (10 mL/19 mL) under Ar(g) was added diethylamine (2.9 mL, 10% v/v) and the reaction mixture stirred at rt for 1 h 50 min. The solvent was removed in vacuo, the crude mixture treated with MeCN (3×20 mL) and the solvent was removed under reduced pressure. The crude amine was then dried under high vacuum for 1 h. Then to a solution of PyBOP (234.9 mg, 0.451 mmol) and FmocGly-OH (133.86 mg, 0.450 mmol) in CH2Cl2 (20 mL) was added diisopropylethylamine (0.25 mL, 1.44 mmol) under Ar(g) with stirring for 3 min. A solution of the resultant deprotected amine of 1 in MeCN (20 mL) was added, and the resulting mixture was allowed to stir at rt for 16 h. The solvent was then removed in vacuo. Purification by flash column chromatography on silica (eluant 1:99-3:97-5:95 MeOH/CH2Cl2) gave a white solid. The material was washed with 1M HCl (aq), dried (MgSO4) and concentrated in vacuo to give 2 (228.6 mg, 0.289 mmol, 68%) as a white solid.

후처리

  1. customThe solvent was removed in vacuo
  2. additionthe crude mixture treated with MeCN (3×20 mL)
  3. customthe solvent was removed under reduced pressure
  4. dry with materialThe crude amine was then dried under high vacuum for 1 h
  5. stirringwith stirring for 3 min
  6. additionwas added
  7. stirringto stir at rt for 16 h
  8. customThe solvent was then removed in vacuo
  9. customPurification by flash column chromatography on silica (eluant 1:99-3:97-5:95 MeOH/CH2Cl2)
  10. customgave a white solid
  11. washThe material was washed with 1M HCl (aq)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-48eb9fbe6dff47f5bc5c0937581b752b
출처 데이터셋
uspto-grants-2013_12
특허 번호
US08614193B2

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