Ammonia → HCID 178519709, compound

HRID 410164Notes

Reaction equation

HRID 410164 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=1)=[O:11].F[C:20]1[C:25]([C:26]2[N:34]=[CH:33][N:32]=[C:31]3[C:27]=2[N:28]=[CH:29][N:30]3C2CCCCO2)=[CH:24][CH:23]=[CH:22][N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(O)(C(F)(F)F)=O.N>O.C(Cl)Cl.CO.CN(C=O)C>[N:34]1[C:26]([C:25]2[C:20]([O:18][C:15]3[CH:16]=[CH:17][C:12]([C:10]([C:2]4[NH:3][C:4]5[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=5[N:1]=4)=[O:11])=[CH:13][CH:14]=3)=[N:21][CH:22]=[CH:23][CH:24]=2)=[C:27]2[C:31]([NH:30][CH:29]=[N:28]2)=[N:32][CH:33]=1

Participants

11

Reactant 5

HCID 222AmmoniaHCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 44479178HCID 44479178, compoundHCID 59326874(1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone

Product 1

HCID 178519709HCID 178519709, compound

Reagents, catalysts & solvents 5

HCID 962WaterCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A screw cap heavy wall flask was charged with (1H-benzo[d]imidazol-2-yl)(4-hydroxyphenyl)methanone (0.350 g, 1.469 mmol), 6-(2-fluoropyridin-3-yl)-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (0.440 g, 1.469 mmol), cesium carbonate (0.957 g, 2.94 mmol) and DMF (6 mL). The vial was capped and heated to 100° C. After 12 hours, the reaction was allowed to cool to RT and diluted with 20 ml of water. The mixture was extracted (3×) with 10 ml of ethyl acetate. The organic layers were combined and washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and purified by column chromatography on silica gel using a gradient of 20 to 60% EtOAc in hexanes. The pure fractions were combined and reduced under vacuum to give an oily residue. The residue was dissolved in DCM (10 mL) and treated with 1 mL of TFA and a few drops of water. The mixture was allowed to stir at room temperature overnight. 10 ml of 2N ammonia in MeOH was added to the reaction with was reduced in vacuo. The residue was partitioned in water and EtOAc. The organic layer was washed (2×) with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate and reduced. The residue obtained was triturated in 1:1 ethyl acetate:ether and then dried in a vacuum oven to give product as solid. MS (ESI, pos. ion) m/z: 434.0 (M+1). IC50 (uM) +++++.

Workup

  1. customA screw cap heavy wall flask
  2. customThe vial was capped
  3. temperatureto cool to RT
  4. extractionThe mixture was extracted (3×) with 10 ml of ethyl acetate
  5. washwashed (2×) with an aqueous saturated solution of sodium bicarbonate
  6. dry with materialThe organic layer was then dried with sodium sulfate
  7. custompurified by column chromatography on silica gel using a gradient of 20 to 60% EtOAc in hexanes
  8. customto give an oily residue
  9. customThe residue was partitioned in water
  10. washThe organic layer was washed (2×) with an aqueous saturated solution of sodium bicarbonate
  11. dry with materialThe organic layer was then dried with sodium sulfate
  12. customThe residue obtained
  13. customwas triturated in 1:1 ethyl acetate
  14. dry with materialether and then dried in a vacuum oven
  15. customto give product as solid

Sources & evidence

ORD record
ord-7201c7ae62604924afa34ec3ffc177ba
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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