Potassium Hydroxide → 9-((3-phenyl-1H-indol-2-yl)methyl)-9H-purin-6-amine

HRID 243341Notes

Reaction equation

HRID 243341 reaction equation
[C:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9](S(C3C=CC(C)=CC=3)(=O)=O)[C:8]=2[CH2:26][N:27]2[CH:35]=[N:34][C:33]3[C:28]2=[N:29][CH:30]=[N:31][C:32]=3[NH2:36])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[K+]>CO>[C:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][C:8]=2[CH2:26][N:27]2[CH:35]=[N:34][C:33]3[C:28]2=[N:29][CH:30]=[N:31][C:32]=3[NH2:36])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 681569779-((3-phenyl-1-tosyl-1H-indol-2-yl)methyl)-9H-purin-6-amine

Product 1

HCID 601619029-((3-phenyl-1H-indol-2-yl)methyl)-9H-purin-6-amineYield 45%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 9-[3-phenyl-1-(toluene-4-sulfonyl)-1H-indol-2-ylmethyl]-9H-purin-6-ylamine from Example 22 (330 mg, 0.667 mmol) and 2M KOH (1.3 mL) in MeOH (20 mL) was stirred at 70° C. for 5 h. Volatiles were removed under reduced pressure and the resulting residue was diluted with water. The pH of the solution was adjusted to 1 by addition of 1M HCl and then to 8 by addition of a saturated solution of NaHCO3. The aqueous layer was extracted with EtOAc (×3) and the combined organic layers were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-9% MeOH in DCM) affording 162 as a white solid (102 mg, 45%). LCMS: RT 3.79 min [M+H]+ 341.2. 1H NMR (DMSO, 400 MHz): δ 11.31 (1H, s), 8.16 (1H, s), 8.02 (1H, s), 7.64-7.59 (2H, m), 7.57 (1H, d, J=7.96 Hz), 7.50 (2H, t, J=7.96 Hz), 7.43-7.33 (2H, m), 7.24 (2H, s), 7.16 (1H, t, J=7.50 Hz), 7.07 (1H, t, J=7.50 Hz), 5.59 (2H, s)

Workup

  1. customVolatiles were removed under reduced pressure
  2. additionthe resulting residue was diluted with water
  3. additionThe pH of the solution was adjusted to 1 by addition of 1M HCl
  4. additionto 8 by addition of a saturated solution of NaHCO3
  5. extractionThe aqueous layer was extracted with EtOAc (×3)
  6. dry with materialthe combined organic layers were dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-9% MeOH in DCM)

Sources & evidence

ORD record
ord-9313baae0f0d478ea293c8bdb6bf6850
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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