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 875987Notes

Reaction equation

HRID 875987 reaction equation
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

Participants

6

Reactant 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

Product 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)acetonitrileYield 54.6%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
105 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-50e7089de8de45f59dc0cbeb86fe0b36
Source dataset
uspto-grants-2015_03
Patent number
US08980903B2

Reaction notes

Loading…