Diisopropylethylamine → (S)-methyl 3-(3-(benzyloxy)-4-methoxyphenyl)-2-((S)-3-hydroxy-2-(2-morpho linoacetamido)propanamido)propanoate

HRID 58791

반응식

HRID 58791 반응식
[NH2:1][C@@H:2]([CH2:28][OH:29])[C:3]([NH:5][C@@H:6]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:13]=1)[C:7]([O:9][CH3:10])=[O:8])=[O:4].[O:30]1[CH2:35][CH2:34][N:33]([CH2:36][C:37](O)=[O:38])[CH2:32][CH2:31]1.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.O.CCOC(C)=O>[CH2:21]([O:20][C:14]1[CH:13]=[C:12]([CH2:11][C@H:6]([NH:5][C:3](=[O:4])[C@@H:2]([NH:1][C:37](=[O:38])[CH2:36][N:33]2[CH2:34][CH2:35][O:30][CH2:31][CH2:32]2)[CH2:28][OH:29])[C:7]([O:9][CH3:10])=[O:8])[CH:17]=[CH:16][C:15]=1[O:18][CH3:19])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

참가 물질

8

반응물 4

HCID 81531DiisopropylethylamineHCID 4389684-Morpholineacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117690386(S)-methyl 2-((S)-2-amino-3-hydroxypropanamido)-3-(3-(benzyloxy)-4-methoxyphenyl)propanoate

생성물 1

HCID 117690529(S)-methyl 3-(3-(benzyloxy)-4-methoxyphenyl)-2-((S)-3-hydroxy-2-(2-morpho linoacetamido)propanamido)propanoate수율 62.9%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

Crude (S)-methyl 2-((S)-2-amino-3-hydroxypropanamido)-3-(3-(benzyloxy)-4-methoxyphenyl)propanoate (TFA salt, 8.7 mmol) was dissolved in DMF (50 mL) followed by addition of 2-morpholinoacetic acid (1.3 g, 8.7 mmol), HATU (5.0 g, 13.1 mmol) and DIPEA (5.0 mL) at 0° C. with stirring. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. EtOAc (200 mL) and water (200 mL) was added and two layers were separated. The aqueous phase was extracted with EtOAc (100 mL×3) and the combined organic phases were washed with brine (200 mL×3), dried over anhydrous sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel (CH2Cl2/EtOAc/MeOH=20:10:1) to afford (S)-methyl 3-(3-(benzyloxy)-4-methoxyphenyl)-2-((S)-3-hydroxy-2-(2-morpho linoacetamido)propanamido)propanoate (2.9 g, 62% yield).

후처리

  1. stirringstirred for 3 h
  2. customtwo layers were separated
  3. extractionThe aqueous phase was extracted with EtOAc (100 mL×3)
  4. washthe combined organic phases were washed with brine (200 mL×3)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography on silica gel (CH2Cl2/EtOAc/MeOH=20:10:1)

출처 및 근거

ORD 기록
ord-fc56aabb75cf48cb9c07d6af1865017a
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09434761B2

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