Dabco → HCID 178423782, compound

HRID 216758Notes

Reaction equation

HRID 216758 reaction equation
Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[NH:4][CH:5]=[N:6]2.N12CCN(CC1)CC2.[Cl:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[C:35]([CH2:36][OH:37])=[CH:34][C:33]2[C:28](=[C:29]([CH3:38])[CH:30]=[CH:31][CH:32]=2)[N:27]=1.[H-].[Na+]>CS(C)=O.O>[N:10]1[C:2]([O:37][CH2:36][C:35]2[C:26]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=3[Cl:19])=[N:27][C:28]3[C:33]([CH:34]=2)=[CH:32][CH:31]=[CH:30][C:29]=3[CH3:38])=[C:3]2[C:7]([NH:6][CH:5]=[N:4]2)=[N:8][CH:9]=1

Participants

7

Reactant 4

HCID 9237DabcoHCID 24758Sodium hydrideHCID 53592776-ChloropurineHCID 57707772HCID 57707772, compound

Product 1

HCID 178423782HCID 178423782, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

Prepared according to procedure L A mixture of 6-chloropurine (75 mg, 0.49 mmol) and 1,4-diazabicyclo[2.2.2]octane (109 mg, 0.97 mmol) in DMSO (0.5 mL) was stirred at rt for 5 h and was then added via cannula to a mixture of (2-(2-chlorophenyl)-8-methylquinolin-3-yl)-methanol (69 mg, 0.24 mmol) and sodium hydride, 60% dispersion in mineral oil (39 mg, 0.97 mmol) in DMSO (0.5 mL) that had been stirred at rt for 15 min prior to the addition. The mixture was stirred at rt for 3.5 h, cooled to 0° C., and H2O (5 mL) was added carefully. The mixture was extracted with EtOAc (3×10 mL), and the combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting yellow oil was dissolved in CH2Cl2, evaporated onto silica gel (deactivated with 2M NH3 in MeOH), and purified by flash chromatography (Biotage® Si 25+M) eluting with 2M NH3 in MeOH/CH2Cl2 (5%) to provide a white solid [PI3Kδ IC50=25 nM]. MS (ESI+) m/z=402.0 (M+1).

Workup

  1. customPrepared
  2. stirringhad been stirred at rt for 15 min
  3. additionto the addition
  4. stirringThe mixture was stirred at rt for 3.5 h
  5. temperaturecooled to 0° C.
  6. extractionThe mixture was extracted with EtOAc (3×10 mL)
  7. dry with materialthe combined organic layers were dried (MgSO4)
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe resulting yellow oil was dissolved in CH2Cl2
  10. customevaporated onto silica gel (deactivated with 2M NH3 in MeOH)
  11. custompurified by flash chromatography (Biotage® Si 25+M)
  12. washeluting with 2M NH3 in MeOH/CH2Cl2 (5%)
  13. customto provide a white solid [PI3Kδ IC50=25 nM]

Sources & evidence

ORD record
ord-e4ef3448ff5a4ff8b3ddba06b6e38fa2
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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