Triethylamine → {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile

HRID 1617366Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1617366
Cl.Cl.Cl.[NH:4]1[CH2:9][CH2:8][CH:7]([N:10]2[CH2:13][C:12]([CH2:36][C:37]#[N:38])([N:14]3[CH:18]=[C:17]([C:19]4[C:20]5[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:21]=5[N:22]=[CH:23][N:24]=4)[CH:16]=[CH:15]3)[CH2:11]2)[CH2:6][CH2:5]1.[F:39][C:40]1[C:48]([C:49]([F:52])([F:51])[F:50])=[N:47][CH:46]=[CH:45][C:41]=1[C:42](O)=[O:43].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[F:39][C:40]1[C:48]([C:49]([F:52])([F:50])[F:51])=[N:47][CH:46]=[CH:45][C:41]=1[C:42]([N:4]1[CH2:9][CH2:8][CH:7]([N:10]2[CH2:11][C:12]([CH2:36][C:37]#[N:38])([N:14]3[CH:18]=[C:17]([C:19]4[C:20]5[CH:27]=[CH:26][N:25]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:34])([CH3:33])[CH3:35])[C:21]=5[N:22]=[CH:23][N:24]=4)[CH:16]=[CH:15]3)[CH2:13]2)[CH2:6][CH2:5]1)=[O:43]

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 516892Sodium BicarbonateHCID 265964893-Fluoro-2-(trifluoromethyl)isonicotinic acidHCID 67391288{1-piperidin-4-yl-3-[3-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile trihydrochloride

Produkt 1

HCID 67391977{1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A mixture of {1-piperidin-4-yl-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile trihydrochloride (1.22 g, 2.03 mmol), 3-fluoro-2-(trifluoromethyl)isonicotinic acid (460 mg, 2.2 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (1.07 g, 2.42 mmol) and triethylamine (2.0 mL, 14 mmol) in DMF (20.0 mL) was stirred at room temperature overnight. LS-MS showed the reaction was complete. EtOAc (60 mL) and saturated NaHCO3 aqueous solution (60 mL) were added to the reaction mixture. After stirring at room temperature for 10 minutes, the organic phase was separated and the aqueous layer was extracted with EtOAc three times. The combined extracts were washed with brine, dried over anhydrous Na2SO4, filtered and evaporated under reduced pressure. Purification by flash chromatography provided {1-{1-[3-fluoro-2-(trifluoromethyl)isonicotinoyl]piperidin-4-yl}-3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrrol-1-yl]azetidin-3-yl}acetonitrile as a white powder.

Aufarbeitung

  1. stirringAfter stirring at room temperature for 10 minutes
  2. customthe organic phase was separated
  3. extractionthe aqueous layer was extracted with EtOAc three times
  4. washThe combined extracts were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customPurification by flash chromatography

Quellen und Nachweise

ORD-Eintrag
ord-4673dcccf4ce48d789ef093ec9fd50f3
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765734B2

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