Cesium carbonate → HCID 87222480, compound

HRID 712290Notes

Reaction equation

HRID 712290 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[S:8][C:9]2[C:15](/[C:16](/[CH3:20])=[N:17]/[O:18][CH3:19])=[CH:14][C:13]([O:21][S:22]([C:25]([F:28])([F:27])[F:26])(=[O:24])=[O:23])=[CH:12][C:10]=2[N:11]=1)=[O:5])[CH3:2].C(C1(C(OCC)=O)CCN(C2N=CC(C3C=C(/C(/C)=N/OC)C4SC(NC(=O)NCC)=NC=4C=3)=CN=2)CC1)C.B1(B2OCC(C)(C)CO2)OCC(C)(C)CO1.C([O-])(=O)C.[K+].B([O-])[O-].C(OC(C1(CC)CCN(C2N=CC(Br)=CN=2)CC1)=O)C.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]([NH:6][C:7]1[S:8][C:9]2[C:15](/[C:16](/[CH3:20])=[N:17]/[O:18][CH3:19])=[CH:14][C:13]([O:21][S:22]([C:25]([F:26])([F:27])[F:28])(=[O:23])=[O:24])=[CH:12][C:10]=2[N:11]=1)=[O:5])[CH3:2]

Participants

9

Reactant 6

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 2734316Bis(neopentyl glycolato)diboronHCID 66977031HCID 66977031, compoundHCID 87222479HCID 87222479, compoundHCID 178514824HCID 178514824, compound

Product 1

HCID 87222480HCID 87222480, compoundYield 32%

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

Ethyl 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-[(E)-N-methoxy-C-methyl-carbonimidoyl]-1,3-benzothiazol-5-yl]pyrimidin-2-yl]piperidine-4-carboxylate [2-(ethylcarbamoylamino)-7-[(E)-N-methoxy-C-methyl-carbonimidoyl]-1,3-benzothiazol-5-yl]trifluoromethanesulfonate (220 mg, 0.5 mmol), bis-(neopentyl glycolato)diboron (226 mg, 1 mmol) and potassium acetate (147 mg, 1.5 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 (26 mg, 0.05 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 divided into 2 aliquots in reaction tubes. To one of the tubes was added 1-(5-Bromo-pyrimidin-2-yl)-4-ethyl-piperidine-4-carboxylic acid ethyl ester (103 mg, 0.3 mmol), cesium carbonate solution (170 μl, 0.63 mmol, 3.7M aq. soln.) and Pd(dppf)Cl2 (13 mg, 0.025 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 a gradient of petrol-EtOAc 0-100% as the eluent to give the desired compound as an off white solid, 87 mg, 32% 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. customthen divided into 2 aliquots in reaction tubes
  6. additionwere added
  7. customthe reaction sealed
  8. temperatureheated to 90° C. for 3 h at the end of which time LCMS

Sources & evidence

ORD record
ord-2921bb75373941d9905d8a18f24769ca
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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