Acetic Acid → HCID 57707864, compound

HRID 216771Notes

Reaction equation

HRID 216771 reaction equation
[N:1]1[C:6]2[NH:7][CH:8]=[CH:9][C:5]=2[C:4]([O:10][CH2:11][C:12]2[C:13]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[CH3:29])=[N:14][C:15]3[C:20]([CH:21]=2)=[CH:19][CH:18]=[CH:17][C:16]=3[CH3:22])=[N:3][CH:2]=1.C1C=C[NH+]=CC=1.Br[Br-]Br.CC(O)=[O:41]>CC(O)(C)C.[Zn]>[CH3:22][C:16]1[CH:17]=[CH:18][CH:19]=[C:20]2[C:15]=1[N:14]=[C:13]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH3:29])[C:12]([CH2:11][O:10][C:4]1[C:5]3[CH2:9][C:8](=[O:41])[NH:7][C:6]=3[N:1]=[CH:2][N:3]=1)=[CH:21]2

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 57707985HCID 57707985, compound

Product 1

HCID 57707864HCID 57707864, compound

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6386tert-ButanolSolvent

Procedure

To a solution of 3-((7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)methyl)-8-methyl-2-o-tolylquinoline (120 mg, 0.316 mmol) in AcOH (4 mL) and t-BuOH (2.43 mL) under N2 was added pyridinium bromide perbromide (303 mg, 0.947 mmol) in one portion. After stirring at room temperature for 5 h the solvents was removed, and the remaining solids suspended in H2O and extracted with ethyl acetate, after drying with brine and MgSO4 the crude dry solid was dissolved in THF (8 mL) followed by 5 mL of a saturated NH4Cl solution, this was followed in turn by Zn powder (528 mg, 26 mmol) and stirred at room temperature for 24 h. The mixture was then extracted with ethyl acetate and chromatographed {gradient elution DCM/89:9:1 (DCM/MeOH/NH4OH)}. The solid was recrystallized from DCM to provide the pure product [PI3Kδ IC50=349 nM]. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.29 (1H, s), 8.52 (1H, s), 8.30 (1H, s), 7.89 (1H, d, J=7.8 Hz), 7.65 (1H, d, J=7.0 Hz), 7.51-7.57 (1H, m), 7.30-7.35 (3H, m), 7.22-7.29 (1H, m), 3.47 (2H, s), 2.67 (3H, s), 2.09 (3H, s) Mass Spectrum (ESI) m/e=397.1 [M+1].

Workup

  1. customwas removed
  2. extractionextracted with ethyl acetate
  3. dry with materialafter drying with brine and MgSO4 the crude
  4. customdry solid
  5. dissolutionwas dissolved in THF (8 mL)
  6. stirringstirred at room temperature for 24 h
  7. extractionThe mixture was then extracted with ethyl acetate
  8. customchromatographed
  9. wash{gradient elution DCM/89:9:1 (DCM/MeOH/NH4OH)}
  10. customThe solid was recrystallized from DCM
  11. customto provide the pure product [PI3Kδ IC50=349 nM]

Sources & evidence

ORD record
ord-ee35e6a96607423e8852b19987e790dc
Source dataset
uspto-grants-2012_06
Patent number
US08193199B2

Reaction notes

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