Nitrogen → HCID 66977155, compound

HRID 712366Notes

Reaction equation

HRID 712366 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][C:11]([CH2:17][CH3:18])([C:14]([O-:16])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.B1(B2[O:32][C:31]([CH3:34])([CH3:33])[C:30](C)(C)O2)OC(C)(C)C(C)(C)O1.[C:37]([O-])(=O)[CH3:38].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.N#N.Br[C:64]1[CH:69]=[C:68]([N:70]2[CH:74]=[CH:73][CH:72]=[N:71]2)[N:67]2[CH:75]=[C:76]([NH:78][C:79](=[O:81])[O-])[N:77]=[C:66]2[CH:65]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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.CO.C(Cl)Cl>[C:31]([O:32][C:79]([NH:78][C:76]1[N:77]=[C:66]2[CH:65]=[C:64]([C:2]3[CH:3]=[N:4][C:5]([N:8]4[CH2:13][CH2:12][C:11]([CH2:17][CH3:18])([C:14]([O:16][CH2:37][CH3:38])=[O:15])[CH2:10][CH2:9]4)=[N:6][CH:7]=3)[CH:69]=[C:68]([N:70]3[CH:74]=[CH:73][CH:72]=[N:71]3)[N:67]2[CH:75]=1)=[O:81])([CH3:30])([CH3:33])[CH3:34]

Participants

15

Reactant 7

HCID 947NitrogenHCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 86664063HCID 86664063, compoundHCID 86664064HCID 86664064, compound

Product 1

HCID 66977155HCID 66977155, compoundYield 55%

Reagents, catalysts & solvents 7

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
95 °C

Procedure

A solution of 1-(5-bromopyrimidin-2-yl)-4-ethyl-piperidine-4-carboxylate (0.882 g, 2.58 mmol), bis(pinacolato)diboron, (0.818 g, 2.58 mmol), potassium acetate (0.379 g, 3.87 mmol) and tricyclohexylphosphine, 43 mg, 0.15 mmol in dioxane (10 mL) was degassed with N2 for 10 mins. Pd2(dba)3 (71 mg, 0.077 mmol) was introduced and the reaction heated to 95° C. for 2 hours. TLC indicated complete consumption of tarting material. The solution was filtered through celite, the solids washed with 10 mL of dioxane and the combined filtrate added to a separate flask containing N-(7-bromo-5-pyrazol-1-yl-imidazo[1,2-a]pyridin-2-yl)carbamate (0.650 g, 1.72 mmol) and K3PO4 (0.694 g; 3.27 mmol) in dioxane (10 mL) and water (2 mL). The mixture was degassed with N2 for 10 mins then PdCl2(PPh3)2 (92 mg, 0.131 mmol) was added. The mixture was heated under N2 to 85° C. for 3 hours then cooled and diluted with EtOAc (50 mL). The suspension was filtered, yielding a slightly greenish white solid with the requisite molecular ion (MS: 561.05 [M+H]+). The crude was suspended in EtOAc (30 mL) to which was added DCM (20 mL) and MeOH (10 mL), heated until partial dissolution then cooled overnight. The solid was once again filtered, washed with a small amount of EtOAc, then heptane, and dried, giving 0.530 g (55%) of product, which was used directly in the next step without further purification.

Workup

  1. customconsumption of tarting material
  2. filtrationThe solution was filtered through celite
  3. washthe solids washed with 10 mL of dioxane
  4. additionthe combined filtrate added to a separate flask
  5. customThe mixture was degassed with N2 for 10 mins
  6. temperatureThe mixture was heated under N2 to 85° C. for 3 hours
  7. temperaturethen cooled
  8. filtrationThe suspension was filtered
  9. customyielding a slightly greenish white solid with the requisite molecular ion (MS: 561.05 [M+H]+)
  10. temperatureheated until partial dissolution
  11. temperaturethen cooled overnight
  12. filtrationThe solid was once again filtered
  13. washwashed with a small amount of EtOAc
  14. dry with materialheptane, and dried

Sources & evidence

ORD record
ord-135cdb2bef4948c3bc096894219fc231
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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