Potassium Hydroxide → HCID 68283935, compound

HRID 2408703Notes

Reaction equation

HRID 2408703 reaction equation
[CH3:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([CH2:16][CH:17]([C:19]3[CH:20]=[CH:21][C:22]([C:25]#[N:26])=[N:23][CH:24]=3)[OH:18])[C:7]3[CH2:8][CH2:9][N:10]([CH3:15])[CH2:11][C:12]=3[C:13]=2[CH:14]=1.[OH-:27].[K+]>C(O)(C)(C)C>[CH3:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([CH2:16][CH:17]([C:19]3[CH:20]=[CH:21][C:22]([C:25]([NH2:26])=[O:27])=[N:23][CH:24]=3)[OH:18])[C:7]3[CH2:8][CH2:9][N:10]([CH3:15])[CH2:11][C:12]=3[C:13]=2[CH:14]=1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 60197678HCID 60197678, compound

Product 1

HCID 68283935HCID 68283935, compoundYield 15.8%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

5-[2-(3,6-Dimethyl-5,6,7,8-tetrahydro-1,6,9-triaza-fluoren-9-yl)-1-hydroxy-ethyl]-pyridine-2-carbonitrile (600 mg, 1.729 mmol) was dissolved in tert-butanol (12 mL), crushed potassium hydroxide (290 mg, 5.187 mmol) was added, and the mixture heated at 80° C. for 1 h. The reaction was monitored by TLC & LCMS. The reaction mixture was allowed to cool to RT, the solvent was removed under vacuum, and the residue was diluted with water (20 ml) and extracted with EtOAc (2×75 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated to obtain the crude product that was purified by reverse phase chromatography to afford 100 mg of 5-[2-(3,6-dimethyl-5,6,7,8-tetrahydro-1,6,9-triaza-fluoren-9-yl)-1-hydroxy-ethyl]-pyridine-2-carboxylic acid amide. 1H NMR (CD3OD, TFA salt) δ (ppm): 8.62 (s, 1H), 8.1 (s, 1H), 8.05 (d, 1H), 7.95 (d, 1H), 7.8 (s, 1H), 5.23 (t, 1H), 4.7 (d, 1H), 4.53 (d, 1H), 4.4 (m, 2H), 3.83 (m, 1H), 3.6 (m, 1H), 3.4 (m, 2H), 3.2 (s, 3H), 2.43 (s, 3H). Separation by chiral HPLC provides enantiomers II-111a-b.

Workup

  1. additionwas added
  2. temperatureto cool to RT
  3. customthe solvent was removed under vacuum
  4. additionthe residue was diluted with water (20 ml)
  5. extractionextracted with EtOAc (2×75 mL)
  6. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto obtain the crude product that
  9. customwas purified by reverse phase chromatography

Sources & evidence

ORD record
ord-80abcca2e2b04636963de8bf40568cf8
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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