Potassium Hydroxide → HCID 178463583, compound

HRID 243287Notes

Reaction equation

HRID 243287 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[CH:26]([NH:28][C:29]2[N:37]=[CH:36][N:35]=[C:34]3[C:30]=2[N:31]=[CH:32][NH:33]3)[CH3:27])[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[CH:26]([NH:28][C:29]2[N:37]=[CH:36][N:35]=[C:34]3[C:30]=2[N:31]=[CH:32][NH:33]3)[CH3:27])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 178427375HCID 178427375, compound

Product 1

HCID 178463583HCID 178463583, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of {1-[3-phenyl-1-(toluene-4-sulfonyl)-1H-indol-2-yl]ethyl}-(9H-purin-6-yl)amine from Example 21 (200 mg, 0.393 mmol) and 2M KOH (0.8 mL) in MeOH (4 mL) was stirred at 70° C. for 72 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 preparative HPLC (Phenomenex Gemini 5 μm C18 on a gradient 10-98% 0.1% HCO2H in acetonitrile/water) and then by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) affording 116 as a white solid (83 mg, 60%). LCMS: RT 3.98 min [M+H]+ 355.0. 1H NMR (DMSO, 400 MHz): δ 11.29 (1H, s), 8.21-8.09 (2H, m), 7.71-7.55 (3H, m), 7.52-7.42 (5H, m), 7.32 (1H, t, J=7.39 Hz), 7.13 (1H, t, J=7.93 Hz), 7.02 (1H, t, J=7.93 Hz), 5.96 (1H, s), 1.62 (3H, d, J=6.93 Hz)

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 preparative HPLC (Phenomenex Gemini 5 μm C18 on a gradient 10-98% 0.1% HCO2H in acetonitrile/water) and then by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-4c243ec0f913414c9f99bd76bea214b5
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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