Isonicotinic Acid → HCID 68283205, compound

HRID 2408626Notes

Reaction equation

HRID 2408626 reaction equation
[C:1]([OH:9])(=[O:8])[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:16][N:17]1[CH2:43][CH2:42][C:20]2[N:21]([CH2:29][CH:30](OS(C)(=O)=O)[C:31]3[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=3)[C:22]3[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][C:27]=3[C:19]=2[CH2:18]1>CN(C=O)C.O>[CH3:16][N:17]1[CH2:43][CH2:42][C:20]2[N:21]([CH2:29][CH:30]([O:8][C:1](=[O:9])[C:2]3[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=3)[C:31]3[CH:32]=[CH:33][N:34]=[CH:35][CH:36]=3)[C:22]3[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][C:27]=3[C:19]=2[CH2:18]1

Participants

6

Reactant 3

HCID 5922Isonicotinic AcidHCID 11430Potassium CarbonateHCID 86677141HCID 86677141, compound

Product 1

HCID 68283205HCID 68283205, compoundYield 6.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of isonicotinic acid (200 mg, 1.626 mmol) in DMF (10 mL) was added potassium carbonate (560 mg, 4.065 mmol) and stirred the solution at 80° C. for 30 min. Methanesulfonic acid 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethyl ester (455 mg, 1.138 mmol) was added portionwise into the reaction mixture, which was stirred at 80° C. 30 min. The progress of reaction was monitored by LCMS and TLC. The reaction mixture was cooled to RT, diluted with water (30 mL) and extracted with EtOAc (2×50 mL). The combined organic layer was washed with water (4×50 mL), dried over anhydrous sodium sulfate and concentrated. The residue was purified by reverse phase HPLC to yield isonicotinic acid 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethylester (30 mg). 1H NMR (CDCl3, freebase) δ (ppm): 8.79 (d, 2H), 8.58 (d, 2H), 7.77 (d, 2H), 7.23 (d, 1H), 7.18 (s 1H), 7.12 (d, 2H), 7.0 (d, 1H), 6.24 (t, 1H), 4.54 (dd, 1H), 4.35 (dd, 1H), 3.68 (s, 2H), 2.76 (t, 2H), 2.61 (m, 1H), 2.51 (s, 3H), 2.43 (s, 3H), 2.43 (m, 1H). Separation by chiral HPLC provided enantiomers 147a and 147b.

Workup

  1. stirringwas stirred at 80° C
  2. custom30 min
  3. customThe progress of reaction
  4. temperatureThe reaction mixture was cooled to RT
  5. extractionextracted with EtOAc (2×50 mL)
  6. washThe combined organic layer was washed with water (4×50 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-b91a251482d14b34a77aab5ad77a19d5
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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