Cesium carbonate → HCID 89938206, compound

HRID 2200372Notes

Reaction equation

HRID 2200372 reaction equation
[N:1]1([C@@H:7]2[CH2:11][CH2:10][C:9]([C:12]#[N:13])=[CH:8]2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:63]1[CH:72]=[CH:71][C:66]([C:67]([NH:69][CH3:70])=[O:68])=[C:65]([F:73])[CH:64]=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:12]([C:9]1[CH2:10][CH2:11][C@@H:7]([N:1]2[CH2:6][CH2:5][N:4]([C:63]3[CH:72]=[CH:71][C:66]([C:67]([NH:69][CH3:70])=[O:68])=[C:65]([F:73])[CH:64]=3)[CH2:3][CH2:2]2)[CH:8]=1)#[N:13]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 24694329Benzamide, 4-bromo-2-fluoro-N-methyl-HCID 89924032HCID 89924032, compound

Product 1

HCID 89938206HCID 89938206, compoundYield 29.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of (R)-3-(piperazin-1-yl)cyclopent-1-enecarbonitrile (0.500 g, 2.82 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (XANTPHOS) (0.326 g, 0.564 mmol), palladium (II) acetate (Pd(OAc)2) (63.3 mg, 0.282 mmol) and cesium carbonate (1.838 g, 5.64 mmol) in toluene (15 ml) was added 4-bromo-2-fluoro-N-methylbenzamide (WO2006064251, 0.500 g, 2.82 mmol). The reaction mixture was heated to 110° C. for 16 h. The progress of the reaction was monitored by TLC. The reaction mixture was cooled to 25° C. and filtered through celite. The filtrated was concentrated under reduced pressure to obtain a crude product, which was purified by column chromatography over silica gel (100-200 mesh) using 1-5% methanol in dichloromethane as an eluent to obtain the title compound (0.270 g, 29.1%).

Workup

  1. temperatureThe reaction mixture was cooled to 25° C.
  2. filtrationfiltered through celite
  3. concentrationThe filtrated was concentrated under reduced pressure
  4. customto obtain a crude product, which
  5. customwas purified by column chromatography over silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-f02736e8de27419abc7f013a23e8e2aa
Source dataset
uspto-grants-2016_06
Patent number
US09359367B2

Reaction notes

Loading…