Ethylenediamine → 4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[4-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carboxamide

HRID 1617355Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1617355
[C:1]([CH2:3][C:4]1([N:28]2[CH:32]=[C:31]([C:33]3[C:34]4[CH:41]=[CH:40][N:39](COCC[Si](C)(C)C)[C:35]=4[N:36]=[CH:37][N:38]=3)[CH:30]=[N:29]2)[CH2:7][N:6]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[C:24]([F:27])([F:26])[F:25])=[O:15])[CH2:10][CH2:9]2)[CH2:5]1)#[N:2].C(N)CN>FC(F)(F)C(O)=O.C(Cl)Cl>[C:1]([CH2:3][C:4]1([N:28]2[CH:32]=[C:31]([C:33]3[C:34]4[CH:41]=[CH:40][NH:39][C:35]=4[N:36]=[CH:37][N:38]=3)[CH:30]=[N:29]2)[CH2:7][N:6]([CH:8]2[CH2:13][CH2:12][N:11]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[C:24]([F:25])([F:27])[F:26])=[O:15])[CH2:10][CH2:9]2)[CH2:5]1)#[N:2]

Komponenten

5

Edukt 2

HCID 3301EthylenediamineHCID 584314324-{3-(cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[4-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carboxamide

Produkt 1

HCID 584313004-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[4-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 6422Trifluoroacetic acidLösungsmittel

Versuchsvorschrift

4-{3-(Cyanomethyl)-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[4-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carboxamide (210 mg, 0.3 mmol) was dissolved in a 50 M solution of trifluoroacetic acid in methylene chloride (20 mL). After being stirred at room temperature for one hour, the solvents were removed under reduced pressure. The residue was dissolved in methanol (20 mL) and ethylenediamine (1.0 g, 17 mmol). After being stirred at room temperature for one hour, the mixture was purified by HPLC (method B) to give 4-{3-(cyanomethyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}-N-[4-fluoro-2-(trifluoromethyl)phenyl]piperidine-1-carboxamide as a white powder. LC-MS: 568.1 (M+H)+. 1H NMR (400 MHz, DMSO-d6): δ 12.10 (s, 1H), 8.76 (s, 1H), 8.63 (s, 1H), 8.36 (s, 1H), 8.18 (s, 1H), 7.55 (d, J=3.6 Hz, 1H), 7.50 (m, 1H), 7.43 (m, 1H), 7.34 (m, 1H), 7.01 (d, J=3.6 Hz, 1H), 3.79 (m, 2H), 3.67 (d, J=8 Hz, 2H), 3.51 (m, 4H), 2.92 (m, 2H), 2.38 (m, 1H), 1.62 (m, 2H), 1.09 (m, 2H).

Aufarbeitung

  1. customthe solvents were removed under reduced pressure
  2. dissolutionThe residue was dissolved in methanol (20 mL)
  3. stirringAfter being stirred at room temperature for one hour
  4. customthe mixture was purified by HPLC (method B)

Quellen und Nachweise

ORD-Eintrag
ord-0f6711ec68774c8d9517c068a37f36ad
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765734B2

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