Cesium carbonate → HCID 86663996, compound

HRID 712283Notes

Reaction equation

HRID 712283 reaction equation
[CH2:1]([NH:3][C:4]([C:6]1[C:14]2[S:13][C:12]([NH:15][C:16](=[O:20])[NH:17][CH2:18][CH3:19])=[N:11][C:10]=2[CH:9]=[C:8](OS(C(F)(F)F)(=O)=O)[CH:7]=1)=[O:5])[CH3:2].B1(B2OCC(C)(C)CO2)OCC(C)(C)CO1.C([O-])(=O)C.[K+].B([O-])[O-].[CH2:53]([O:55][C:56]([C:58]1([CH2:71]C)[CH2:63][CH2:62][N:61]([C:64]2[N:69]=[CH:68][C:67](Br)=[CH:66][N:65]=2)[CH2:60][CH2:59]1)=[O:57])[CH3:54].C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[CH2:1]([NH:3][C:4]([C:6]1[C:14]2[S:13][C:12]([NH:15][C:16](=[O:20])[NH:17][CH2:18][CH3:19])=[N:11][C:10]=2[CH:9]=[C:8]([C:67]2[CH:66]=[N:65][C:64]([N:61]3[CH2:62][CH2:63][C:58]([CH3:71])([C:56]([O:55][CH2:53][CH3:54])=[O:57])[CH2:59][CH2:60]3)=[N:69][CH:68]=2)[CH:7]=1)=[O:5])[CH3:2]

Participants

9

Reactant 6

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 66977031HCID 66977031, compoundHCID 86663997HCID 86663997, compoundHCID 178514824HCID 178514824, compound

Product 1

HCID 86663996HCID 86663996, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

[7-(Ethylcarbamoyl)-2-(ethylcarbamoylamino)-1,3-benzothiazol-5-yl]trifluoromethanesulfonate (150 mg, 0.344 mmol), bis-(neopentyl glycolato)diboron (155 mg, 0.688 mmol) and potassium acetate (100 mg, 0.89 mmol) were weighed into a Kymax tube. DMF (4 mL) was added and the mixture degassed by bubbling N2 through for 15 min. Pd(dppf)Cl2 (28 mg, 0.0344 mmol) was added and the reaction sealed and heated to 80° C. for 3 h at the end of which time LCMS indicated clean boronate formation. The reaction was allowed to cool to ambient temperature then 1-(5-bromo-pyrimidin-2-yl)-4-ethyl-piperidine-4-carboxylic acid ethyl ester (169 mg, 0.516 mmol), cesium carbonate solution (185 μl, 0.688 mmol, 3.7M aq. soln.) and Pd(dppf)Cl2 (28 mg, 0.0344 mmol) were added and the reaction sealed and heated to 90° C. for 3 h at the end of which time LCMS indicated formation of the desired product. The reaction mixture was diluted with EtOAc, washed with water then brine and the organic layer dried (MgSO4), filtered and the solvent was removed in vacuo. The crude material obtained was purified by flash chromatography on silica gel using DCM:MeOH 96:4 as eluent. The product was obtained as a pale brown solid, 78 mg, 42% yield.

Workup

  1. customthe mixture degassed
  2. customby bubbling N2 through for 15 min
  3. customthe reaction sealed
  4. temperatureto cool to ambient temperature
  5. customthe reaction sealed
  6. temperatureheated to 90° C. for 3 h at the end of which time LCMS

Sources & evidence

ORD record
ord-ca5343a5a6d3479bb15196d0d26c856e
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

Loading…