Cesium carbonate → HCID 71143599, compound

HRID 2363308Notes

Reaction equation

HRID 2363308 reaction equation
C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl.Cl.[CH3:49][Si:50]([CH3:77])([CH3:76])[CH2:51][CH2:52][O:53][CH2:54][N:55]1[C:59]2[N:60]=[CH:61][N:62]=[C:63]([C:64]3[CH:65]=[N:66][N:67]([C:69]4([CH2:73][C:74]#[N:75])[CH2:72][NH:71][CH2:70]4)[CH:68]=3)[C:58]=2[CH:57]=[CH:56]1.Cl[C:79]1[N:80]=[CH:81][C:82]([C:85]([O:87][CH3:88])=[O:86])=[N:83][CH:84]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:74]([CH2:73][C:69]1([N:67]2[CH:68]=[C:64]([C:63]3[C:58]4[CH:57]=[CH:56][N:55]([CH2:54][O:53][CH2:52][CH2:51][Si:50]([CH3:76])([CH3:49])[CH3:77])[C:59]=4[N:60]=[CH:61][N:62]=3)[CH:65]=[N:66]2)[CH2:70][N:71]([C:79]2[N:80]=[CH:81][C:82]([C:85]([O:87][CH3:88])=[O:86])=[N:83][CH:84]=2)[CH2:72]1)#[N:75]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 634876Binap, (A+-)-HCID 67391464{3-[4-(7-{[2-(Trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile dihydrochloride

Product 1

HCID 71143599HCID 71143599, compoundYield 56.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

(R)-(+)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (0.065 g, 0.10 mmol) was added to a mixture of {3-[4-(7-{[2-(trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]azetidin-3-yl}acetonitrile dihydrochloride (0.50 g, 1.0 mmol), methyl 5-chloropyrazine-2-carboxylate (0.18 g, 1.0 mmol)(Ark Pharm, Inc., Cat. #: AK-23920), and cesium carbonate (1.0 g, 3.1 mmol) in toluene (15.0 mL) under nitrogene, followed by palladium acetate (0.023 g, 0.10 mmol). The reaction mixture was stirred at 120° C. for 3 h. After cooled to r.t., the reaction mixture was filtered throught a pad of celite, washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in dichloromethane (0-70%) to afford the desired product (0.31 g, 55%). LCMS (M+H)+: m/z=546.3.

Workup

  1. temperatureAfter cooled to r.t.
  2. filtrationthe reaction mixture was filtered
  3. washwashed with ethyl acetate
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in dichloromethane (0-70%)

Sources & evidence

ORD record
ord-56af19ccd8004b5ca88959873309e342
Source dataset
uspto-grants-2014_04
Patent number
US08691807B2

Reaction notes

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