Dabco → HCID 178424198, compound

HRID 2044836Notes

Reaction equation

HRID 2044836 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.[CH3:19][C:20]1[CH:21]=[CH:22][CH:23]=[C:24]2[C:29]=1[N:28]=[C:27]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH3:36])[C:26]([CH2:37][OH:38])=[CH:25]2.[H-].[Na+]>CS(C)=O.[Cl-].[Na+].O.C(O)(=O)C>[N:10]1[C:2]([O:38][CH2:37][C:26]2[C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[CH3:36])=[N:28][C:29]3[C:24]([CH:25]=2)=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:19])=[C:3]2[C:7]([NH:6][CH:5]=[N:4]2)=[N:8][CH:9]=1

Participants

8

Reactant 4

HCID 9237DabcoHCID 24758Sodium hydrideHCID 53592776-ChloropurineHCID 57707986(8-Methyl-2-o-tolylquinolin-3-yl)methanol

Product 1

HCID 178424198HCID 178424198, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

Prepared according to procedure L A mixture of 6-chloropurine (110 mg, 0.71 mmol) and 1,4-diazabicyclo[2.2.2]octane (160 mg, 1.43 mmol) in DMSO (0.7 mL) was stirred at rt for 4 h and was then added via cannula to a mixture of (8-methyl-2-o-tolylquinolin-3-yl)methanol (94 mg, 0.36 mmol) and sodium hydride, 60% dispersion in mineral oil (57 mg, 1.43 mmol) in DMSO (1 mL) that had been stirred at rt for 15 min prior to the addition. The mixture was stirred at rt for 3.5 h, neutralized by the addition of glacial acetic acid, diluted with brine (15 mL), and extracted with EtOAc (3×15 mL). 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 2 M NH3 in MeOH/CH2Cl2 (5%) to provide a white solid [PI3Kδ IC50=27 nM]. MS (APCI+) m/z=282.3 (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. extractionextracted with EtOAc (3×15 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe resulting yellow oil was dissolved in CH2Cl2
  9. customevaporated onto silica gel (deactivated with 2M NH3 in MeOH)
  10. custompurified by flash chromatography (Biotage® Si 25+M)
  11. washeluting with 2 M NH3 in MeOH/CH2Cl2 (5%)
  12. customto provide a white solid [PI3Kδ IC50=27 nM]

Sources & evidence

ORD record
ord-dc5fb4b2da8846319ffae8a2e1476a3f
Source dataset
uspto-grants-2013_11
Patent number
US08586739B2

Reaction notes

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