Cesium carbonate → (1-(6-((9-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-4-piperidinyl)acetonitrile

HRID 79158

Reaktionsgleichung

Reaktionsgleichung von HRID 79158
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:50]1[N:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][CH:59]([CH2:62][C:63]#[N:64])[CH2:58][CH2:57]2)=[CH:52][CH:51]=1.[CH:65]1([N:70]2[C:74]3[N:75]=[C:76]([NH2:79])[N:77]=[CH:78][C:73]=3[C:72]3[CH:80]=[CH:81][N:82]=[C:83]([F:84])[C:71]2=3)[CH2:69][CH2:68][CH2:67][CH2:66]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:65]1([N:70]2[C:74]3[N:75]=[C:76]([NH:79][C:50]4[N:55]=[CH:54][C:53]([N:56]5[CH2:61][CH2:60][CH:59]([CH2:62][C:63]#[N:64])[CH2:58][CH2:57]5)=[CH:52][CH:51]=4)[N:77]=[CH:78][C:73]=3[C:72]3[CH:80]=[CH:81][N:82]=[C:83]([F:84])[C:71]2=3)[CH2:66][CH2:67][CH2:68][CH2:69]1

Komponenten

6

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 582996889-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineHCID 86654439(1-(6-Chloro-3-pyridinyl)-4-piperidinyl)acetonitrile

Produkt 1

HCID 67234663(1-(6-((9-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-pyridinyl)-4-piperidinyl)acetonitrileAusbeute 54,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

To tris(dibenzylideneacetone)dipalladium (0) (0.0147 g, 0.0160 mmol), xantphos (0.0186 g, 0.0321 mmol), Cs2CO3 (0.0975 g, 0.299 mmol), 2-(1-(6-chloropyridin-3-yl)piperidin-4-yl)acetonitrile (0.0504 g, 0.214 mmol), and compound 245 (0.0580 g, 0.214 mmol) was added degassed (Ar) dioxane (1.0 mL). The reaction was stirred at 105° C. overnight. After 16 h, the reaction was cooled to room temperature and loaded directly onto silica gel. Crystallization from THF and HCl salt formation provided compound 252 (55 mg). 1H NMR (400 MHz, DMSO-d6) δ 1.43 (d, J=10.56 Hz, 2 H) 1.66-1.81 (m, 2 H) 1.86 (d, J=11.35 Hz, 3 H) 2.05 (d, J=6.26 Hz, 2 H) 2.15 (br. s., 2 H) 2.19-2.31 (m, 2 H) 2.59 (d, J=5.87 Hz, 2 H) 2.85 (t, J=11.74 Hz, 2 H) 3.75 (d, J=12.13 Hz, 2 H) 5.53 (quin, J=9.10 Hz, 1 H) 7.68 (d, J=9.39 Hz, 1 H) 8.00 (br. s., 1 H) 8.15 (d, J=5.09 Hz, 1 H) 8.20 (dd, J=9.39, 2.74 Hz, 1 H) 8.30 (dd, J=4.89, 2.93 Hz, 1 H) 9.55 (s, 1 H) 11.80 (br. s., 1 H) ppm.

Aufarbeitung

  1. customdegassed (Ar) dioxane (1.0 mL)
  2. waitAfter 16 h
  3. temperaturethe reaction was cooled to room temperature
  4. customCrystallization from THF and HCl salt formation

Quellen und Nachweise

ORD-Eintrag
ord-180c6528b64449868d97d93dd7bc3a97
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841312B2

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