Diisopropylethylamine → (S)-3-cyano-N-((S)-1-(((S)-3-(cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-2-(2-morpholinoacetamido)propanamide

HRID 58802

Reaktionsgleichung

Reaktionsgleichung von HRID 58802
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.[NH2:34][C@@H:35]([CH2:65][C:66]#[N:67])[C:36]([NH:38][C@@H:39]([CH2:56][C:57]1[CH:62]=[CH:61][C:60]([O:63][CH3:64])=[CH:59][CH:58]=1)[C:40]([NH:42][C@@H:43]([CH2:50][C:51]1[CH2:55][CH2:54][CH2:53][CH:52]=1)[C:44]([C@@:46]1([CH3:49])[CH2:48][O:47]1)=[O:45])=[O:41])=[O:37].[O:68]1[CH2:73][CH2:72][N:71]([CH2:74][C:75](O)=[O:76])[CH2:70][CH2:69]1>CN(C=O)C.O.CCOC(C)=O>[C:66]([CH2:65][C@H:35]([NH:34][C:75](=[O:76])[CH2:74][N:71]1[CH2:72][CH2:73][O:68][CH2:69][CH2:70]1)[C:36]([NH:38][C@@H:39]([CH2:56][C:57]1[CH:62]=[CH:61][C:60]([O:63][CH3:64])=[CH:59][CH:58]=1)[C:40]([NH:42][C@@H:43]([CH2:50][C:51]1[CH2:55][CH2:54][CH2:53][CH:52]=1)[C:44]([C@@:46]1([CH3:49])[CH2:48][O:47]1)=[O:45])=[O:41])=[O:37])#[N:67]

Komponenten

8

Edukt 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 117690423(S)-2-amino-3-cyano-N-((S)-1-(((S)-3-(cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)propanamide

Produkt 1

HCID 117607852(S)-3-cyano-N-((S)-1-(((S)-3-(cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-2-(2-morpholinoacetamido)propanamideAusbeute 35,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

Sequentially HATU (0.61 g, 1.6 mmol) and DIEA (1.35 mL, 7.8 mmol) were added to a 0° C. solution of (S)-2-amino-3-cyano-N-((S)-1-(((S)-3-(cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)propanamide (1 mmol) and 2-morpholinoacetic acid (160 mg, 1.10 mmol) in DMF (20 mL) with stirring. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. EtOAc (100 mL) and water (100 mL) was added. The two layers were separated and the aqueous phase was extracted with EtOAc (50 mL×3). 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 (EtOAc/hexane=1:2) to afford (S)-3-cyano-N-((S)-1-(((S)-3-(cyclopent-1-en-1-yl)-1-((R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)amino)-3-(4-methoxyphenyl)-1-oxopropan-2-yl)-2-(2-morpholinoacetamido)propanamide (210 mg, 35% yield). 1H NMR (300 MHz, DMSO-d6): δ 8.44 (d, J=6.6 Hz, 1H), 8.16 (d, J=7.5 Hz, 1H), 8.08 (d, J=8.1 Hz, 1H), 7.10 (d, J=8.4 Hz, 2H), 6.78 (d, J=8.4 Hz, 2H), 5.40 (s, 1H), 4.60-4.35 (m, 3H), 3.70 (s, 3H), 3.62-3.57 (m, 4H), 3.18 (m, 1H), 3.05-2.80 (m, 3H), 2.65 (m, 1H), 2.50-2.10 (m, 10H), 1.90-1.70 (m, 2H), 1.37 (s, 3H). MS(EI) for C31H41N5O7, found 596.3 (MH)+.

Aufarbeitung

  1. stirringstirred for 3 h
  2. customThe two layers were separated
  3. extractionthe aqueous phase was extracted with EtOAc (50 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 (EtOAc/hexane=1:2)

Quellen und Nachweise

ORD-Eintrag
ord-255f3b9996e44f99b15a12667cc98a77
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09434761B2

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