Potassium Hydroxide → HCID 68283989, compound

HRID 1469461Notes

Reaction equation

HRID 1469461 reaction equation
[CH3:1][N:2]1[CH2:26][CH2:25][C:5]2[N:6]([CH2:14][CH:15]([C:17]3[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[N:21][CH:22]=3)[OH:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[OH-:27].[K+]>C(O)(C)(C)C>[CH3:1][N:2]1[CH2:26][CH2:25][C:5]2[N:6]([CH2:14][CH:15]([C:17]3[CH:18]=[CH:19][C:20]([C:23]([NH2:24])=[O:27])=[N:21][CH:22]=3)[OH:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

4

Reactant 2

HCID 14797Potassium HydroxideHCID 68284016HCID 68284016, compound

Product 1

HCID 68283989HCID 68283989, compoundYield 12.8%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 5-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-hydroxy-ethyl]-pyridine-2-carbonitrile (1.5 g, 4.3 mmol) in tert-butanol (30 mL) was added crushed KOH (728 mg, 13 mmol) and the reaction mixture was stirred at 80° C. for 1 h. The progress of reaction was monitored by LCMS. The reaction mixture was concentrated. The residue was diluted with water (50 mL) and extracted with EtOAc (2×100 mL). The combined organic layer was washed with water (2×100 mL), dried over anhydrous sodium sulfate and concentrated. The crude material was purified by reverse phase HPLC to yield 5-[2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-hydroxy-ethyl]-pyridine-2-carboxylic acid amide (200 mg). 1H NMR (CDCl3, freebase) δ (ppm): 8.45 (d, 1H), 8.12 (t, 1H), 7.78 (s, 2H), 7.05 (m, 2H), 6.94 (t, 1H), 5.57 (bs, 1H), 5.03 (m, 1H), 4.13 (s, 2H), 3.63 (m, 2H), 2.79 (m, 2H), 2.78 (bs 1H), 2.66 (d, 1H), 2.53 (d, 3H), 2.42 (s, 3H). Separation by chiral HPLC provided enantiomers 144a and 144b.

Workup

  1. customThe progress of reaction
  2. concentrationThe reaction mixture was concentrated
  3. additionThe residue was diluted with water (50 mL)
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe combined organic layer was washed with water (2×100 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe crude material was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-b707195f6ffd4485a6e45672442094fa
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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