Diisopropylethylamine → (S)-2-((S)-2-{(S)-3-(4-Allyloxy-phenyl)-2-[(tert-butoxy-hydroxy-methyl)-amino]-propionylamino}-3-methyl-butyrylamino)-but-3-enoic acid methyl ester

HRID 2371335ノート

反応式

HRID 2371335 の反応式
[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C@H:12]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:13]([NH:15][C@@H:16]([CH:20]([CH3:22])[CH3:21])[C:17](O)=[O:18])=[O:14])=[CH:7][CH:6]=1)[CH:2]=[CH2:3].Cl.[CH3:32][O:33][C:34](=[O:39])[C@@H:35]([NH2:38])[CH:36]=[CH2:37].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH3:32][O:33][C:34](=[O:39])[C@@H:35]([NH:38][C:17](=[O:18])[C@@H:16]([NH:15][C:13](=[O:14])[C@@H:12]([NH:23][CH:24]([O:26][C:27]([CH3:29])([CH3:30])[CH3:28])[OH:25])[CH2:11][C:8]1[CH:9]=[CH:10][C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[CH:6][CH:7]=1)[CH:20]([CH3:22])[CH3:21])[CH:36]=[CH2:37]

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 66847200(S)-2-[(S)-3-(4-Allyloxy-phenyl)-2-tert-butoxycarbonylamino-propionylamino]-3-methyl-butyric acidHCID 86650247(S)-Methyl 2-aminobut-3-enoate hydrochloride

生成物 1

HCID 66847466(S)-2-((S)-2-{(S)-3-(4-Allyloxy-phenyl)-2-[(tert-butoxy-hydroxy-methyl)-amino]-propionylamino}-3-methyl-butyrylamino)-but-3-enoic acid methyl ester

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Acid 43 (1.03 g, 2.45 mmol), amine 63 (1.1 equiv) and HATU (1.1 equiv) were dissolved in anhydrous DMF (0.10-0.50M relative to acid). DIPEA was added (4 equiv) and the reaction mixture stirred at rt for 18 h. This was partitioned between EtOAc and 1M hydrochloric acid. The organic phase was washed sequentially with 1M hydrochloric acid and brine before being dried (MgSO4), filtered and concentrated in vacuo. The crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether to yield a white solid, 0.964 g, 76%. Rf=0.46 (1/1 EtOAc/(50/70) petroleum ether). m.p. 104-106° C.

後処理

  1. customThis was partitioned between EtOAc and 1M hydrochloric acid
  2. washThe organic phase was washed sequentially with 1M hydrochloric acid and brine
  3. dry with materialbefore being dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography on silica using a gradient of EtOAc and (50/70) petroleum ether
  7. customto yield a white solid, 0.964 g, 76%

出典と根拠

ORDレコード
ord-67f1990d654241a1aae78a405ab818c7
出典データセット
uspto-grants-2014_04
特許番号
US08710178B2

反応ノート

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