Cesium carbonate → HCID 86712670, compound

HRID 1779017Notes

Reaction equation

HRID 1779017 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][C:17]([O:19]C)=[O:18])[C:5]([CH3:21])=[CH:4][N:3]=1.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([CH:29]2[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31][CH2:30]2)=[CH:25][CH:24]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O[Li].O>O1CCOCC1.CN(C=O)C.CCN(CC)CC.C1COCC1.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].[Pd].O.CO.CCOC(C)=O>[C:38]([O:37][C:35]([N:32]1[CH2:33][CH2:34][CH:29]([C:26]2[CH:27]=[CH:28][C:23]([NH:22][C:2]3[N:7]=[C:6]([CH2:8][CH2:9][C:10]4[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=4[CH2:16][C:17]([OH:19])=[O:18])[C:5]([CH3:21])=[CH:4][N:3]=3)=[CH:24][CH:25]=2)[CH2:30][CH2:31]1)=[O:36])([CH3:41])([CH3:39])[CH3:40]

Participants

15

Reactant 5

HCID 10796Cesium carbonateHCID 168937Lithium hydroxide, monohydrateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21940085tert-Butyl 4-(4-aminophenyl)piperidine-1-carboxylateHCID 86712625HCID 86712625, compound

Product 1

HCID 86712670HCID 86712670, compound

Reagents, catalysts & solvents 9

HCID 23938PalladiumCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of methyl 2-(2-((2-chloro-5-methylpyrimidin-4-yl)ethynyl)phenyl)acetate (K7) (110 mg, 0.366 mmol) in 1,4-dioxane (5 mL) was added tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate (101 mg, 0.366 mmol), Cs2CO3 (477 mg, 1.46 mmol), Pd2(dba)3 (33 mg, 0.037 mmol) and Xantphos (63 mg, 0.11 mmol). The resulting suspension was degassed with nitrogen for 5 minutes then heated under microwave irradiation for 30 minutes at 120° C. The volatiles were removed under reduced pressure and the residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.) to give a yellow oil. A suspension of 10% Pd/C (100 mg) in DMF (10 mL) and Et3N (1 mL) was added and the resulting mixture stirred under an atmosphere of hydrogen for 16 hours. EtOAc (60 mL) was added and the resulting mixture filtered through Celite. The filtrate was evaporated under reduced pressure and the residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridges, 0-60% EtOAc in petroleum benzine 40-60° C.) to give a yellow oil. This was taken up in THF (7 mL), MeOH (7 mL) and H2O (1.5 mL) to which LiOH.H2O (115 mg, 2.74 mmol) was added. The resulting mixture was stirred at room temperature overnight then the volatiles were removed under reduced pressure. The residue was partitioned between EtOAc (50 mL) and aqueous HCl (2 M; 50 mL) then the layers were separated. The aqueous phase was extracted with EtOAc (2×50 mL) then the organics were combined, washed with brine and dried over MgSO4. The volatiles were removed in vacuo to give the title compound A55 as yellow oil (127 mg, 87%); LCMS-A: rt 6.272 min; m/z 531 [M+H]+.

Workup

  1. customThe resulting suspension was degassed with nitrogen for 5 minutes
  2. customThe volatiles were removed under reduced pressure
  3. custompurified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-50% EtOAc in petroleum benzine 40-60° C.)
  4. customto give a yellow oil
  5. additionwas added
  6. filtrationthe resulting mixture filtered through Celite
  7. customThe filtrate was evaporated under reduced pressure
  8. custompurified by column chromatography (Biotage Isolera, SiO2 cartridges, 0-60% EtOAc in petroleum benzine 40-60° C.)
  9. customto give a yellow oil
  10. stirringThe resulting mixture was stirred at room temperature overnight
  11. customthe volatiles were removed under reduced pressure
  12. customThe residue was partitioned between EtOAc (50 mL) and aqueous HCl (2 M; 50 mL)
  13. customthe layers were separated
  14. extractionThe aqueous phase was extracted with EtOAc (2×50 mL)
  15. washwashed with brine
  16. dry with materialdried over MgSO4
  17. customThe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-0b17585c43004fa187ddee66852a063b
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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