Diisopropylethylamine → 3-(4-((2-(1H-imidazol-5-yl)acetamido)methyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamate

HRID 216093

Reaktionsgleichung

Reaktionsgleichung von HRID 216093
[NH:1]1[C:5]([CH2:6][C:7]([OH:9])=O)=[CH:4][N:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH3:43][N:44]([CH3:75])[C:45](=[O:74])[O:46][C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([NH:53][C:54]([C:56]2([CH2:72][NH2:73])[CH2:61][CH2:60][N:59]([C:62]3[C:63]4[C:70]([CH3:71])=[CH:69][NH:68][C:64]=4[N:65]=[CH:66][N:67]=3)[CH2:58][CH2:57]2)=[O:55])[CH:48]=1>C(Cl)Cl.O>[CH3:75][N:44]([CH3:43])[C:45](=[O:74])[O:46][C:47]1[CH:52]=[CH:51][CH:50]=[C:49]([NH:53][C:54]([C:56]2([CH2:72][NH:73][C:7](=[O:9])[CH2:6][C:5]3[NH:1][CH:2]=[N:3][CH:4]=3)[CH2:57][CH2:58][N:59]([C:62]3[C:63]4[C:70]([CH3:71])=[CH:69][NH:68][C:64]=4[N:65]=[CH:66][N:67]=3)[CH2:60][CH2:61]2)=[O:55])[CH:48]=1

Komponenten

7

Edukt 4

HCID 81531Diisopropylethylamine2×HCID 96215Imidazole-4-acetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 56962369Lx-7101

Produkt 1

HCID 444821143-(4-((2-(1H-imidazol-5-yl)acetamido)methyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamateAusbeute 72 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel3×

Versuchsvorschrift

To a suspension of 2-(1H-imidazol-5-yl)acetic acid (0.238 g, 1.47 mmol) and HATU (0.372 g, 0.978 mmol) in CH2Cl2 (5 mL) was added N,N-diisopropylethylamine (0.51 mL, 2.93 mmol). The resulting solution was allowed to stir for 20 min. at room temperature. To this solution was added the acetate salt of 3-(4-(aminomethyl)-1-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamido)phenyl dimethylcarbamate (from example 20, 0.500 g, 0.978 mmol) and N,N-diisopropylethylamine (0.17 mL) in CH2Cl2 (5 mL). The reaction was allowed to stir at room temperature for 6h, and then diluted with H2O (10 mL) and CH2Cl2 (20mL). The mixture was extracted with CH2Cl2 (2×10 mL), and the combined organics were washed with NaHCO3 (10 mL) and brine (10 mL), dried over MgSO4, and concentrated under vacuum. The residue was purified by flash chromatography (3-10% MeOH:CH2Cl2) to afford the title compound (0.393 g, 72% yield) as a white solid. This solid was suspended in water, and acetic acid was added until the solution became clear. This solution was frozen and lyophilized to the di-acetate salt of the title compound (0.477 g).

Aufarbeitung

  1. extractionThe mixture was extracted with CH2Cl2 (2×10 mL)
  2. washthe combined organics were washed with NaHCO3 (10 mL) and brine (10 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by flash chromatography (3-10% MeOH:CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-71224663e6224a029a18263a351951d2
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193202B2

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