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

HRID 1915972

反応式

HRID 1915972 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: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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒HCID 21877088Acetonitrile methylene chloride溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-48eb9fbe6dff47f5bc5c0937581b752b
出典データセット
uspto-grants-2013_12
特許番号
US08614193B2

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