Cesium carbonate → HCID 53380231, compound

HRID 1771542Notes

Reaction equation

HRID 1771542 reaction equation
Cl[C:2]1[CH:7]=[C:6](Cl)[N:5]=[C:4]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[N:3]=1.[N:15]1[CH:20]=[CH:19][CH:18]=[C:17](B(O)O)[CH:16]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH:30]1([NH:33][C:34](=[O:51])[NH:35][C:36]2[CH:41]=[CH:40][C:39](B3OC(C)(C)C(C)(C)O3)=[CH:38][CH:37]=2)[CH2:32][CH2:31]1>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:30]1([NH:33][C:34]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([C:2]3[CH:7]=[C:6]([C:17]4[CH:16]=[N:15][CH:20]=[CH:19][CH:18]=4)[N:5]=[C:4]([N:9]4[CH2:14][CH2:13][O:12][CH2:11][CH2:10]4)[N:3]=3)=[CH:38][CH:37]=2)=[O:51])[CH2:32][CH2:31]1

Participants

8

Reactant 4

HCID 10796Cesium carbonate2×HCID 27343783-Pyridinylboronic acidHCID 27720684-(4,6-Dichloropyrimidin-2-yl)morpholineHCID 44119149N-Cyclopropyl-N'-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea

Product 1

HCID 53380231HCID 53380231, compound

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

4-(4,6-dichloropyrimidin-2-yl)morpholine (100 mg 0.43 mmol), pyridine-3-boronic acid (49 mg, 0.4 mmol), Cs2CO3 (280 mg, 0.86 mmol) and Pd(PPh3)2Cl2 (20 mg, 0.025 mmol) were combined in dioxane (3 ml) and water (1 ml). The reaction mixture was then heated by microwave at 120° C. for 20 min. Without purification (4-(3-cyclopropylureido)phenyl)boronic acid pinacol ester (130 mg, 0.43 mmol), Cs2CO3 (280 mg, 0.86 mmol) and Pd(PPh3)2Cl2 (20 mg, 0.025 mmol) were added and the reaction mixture was then heated by microwave at 120° C. for a further 20 min. The reaction mixture was partitioned between EtOAc and water. The organic layer was passed through a PTFE hydrophobic frit and the solvent removed in vacuo. Residual solid was triturated to give crude produect which was further purifed by prep LC/MS (low pH) to yield (9 mg, 5%).

Workup

  1. additionwere added
  2. temperaturethe reaction mixture was then heated by microwave at 120° C. for a further 20 min
  3. customThe reaction mixture was partitioned between EtOAc and water
  4. customthe solvent removed in vacuo
  5. customResidual solid was triturated
  6. customto give crude produect which
  7. customto yield (9 mg, 5%)

Sources & evidence

ORD record
ord-37cca4ce0b924f0a83baa8bf281d5d89
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

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