3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrile → 3-[1-(8-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-1,2,3,6-tetrahydro-pyridin-4-yl]-1H-indole-5-carbonitrile

HRID 1823839

Reaction equation

HRID 1823839 reaction equation
[NH:1]1[CH2:6][CH:5]=[C:4]([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:16]#[N:17])[CH:14]=3)[NH:9][CH:8]=2)[CH2:3][CH2:2]1.[CH3:18][O:19][C:20]1[C:25]2[O:26][C@H:27]([CH2:30]C3C=C(C)C=CC=3S([O-])(=O)=O)[CH2:28][O:29][C:24]=2[CH:23]=[CH:22][CH:21]=1>CN(C)C=O.O1CCCC1.C(=O)(O)[O-].[Na+]>[CH3:18][O:19][C:20]1[C:25]2[O:26][CH:27]([CH2:30][N:1]3[CH2:2][CH:3]=[C:4]([C:7]4[C:15]5[C:10](=[CH:11][CH:12]=[C:13]([C:16]#[N:17])[CH:14]=5)[NH:9][CH:8]=4)[CH2:5][CH2:6]3)[CH2:28][O:29][C:24]=2[CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 2

HCID 113335543-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrileHCID 86586596(2R)-8-methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl-4-methylbenzenesulfonate

Product 1

HCID 102723843-[1-(8-Methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-1,2,3,6-tetrahydro-pyridin-4-yl]-1H-indole-5-carbonitrileYield 56.6%

Reagents, catalysts & solvents 2

HCID 516892Sodium BicarbonateSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

3-(1,2,3,6-Tetrahydro-4-pyridinyl)1H-indole-5-carbonitrile (0.70 g, 3.1 mmole) and [(2R)-8-methoxy-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl-4-methylbenzenesulfonate (040 g, 1.1 mmole) were dissolved in a mixture of dimethylformamide/tetrahydrofuran (1:1 v/v, 50 mL) and sodium bicarbonate (1.0 g) added. The reaction mixture was refluxed under nitrogen for 18 hours. The solvent was evaporated in vacuum and the residue partitioned between 400 mL each of methylene chloride and water. The organic phase was separated, washed with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered. The filtrate was evaporated in vacuum to give a solid which was purified by column chromatography on silica gel. Elution with 2% methanol in chloroform, concentration of the product fractions in vacuum and treatment of an ethereal solution of the residue with 4 N isopropanolic HCl gave the (S)-enantiomer of the title compound (250 mg, 54%) as a yellow solid hydrochloride, one-quarter hydrate, m.p. 235–238° C.

Workup

  1. additionadded
  2. temperatureThe reaction mixture was refluxed under nitrogen for 18 hours
  3. customThe solvent was evaporated in vacuum
  4. customthe residue partitioned between 400 mL each of methylene chloride and water
  5. customThe organic phase was separated
  6. washwashed with water and saturated aqueous sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customThe filtrate was evaporated in vacuum
  10. customto give a solid which
  11. customwas purified by column chromatography on silica gel
  12. washElution with 2% methanol in chloroform, concentration of the product fractions in vacuum and treatment of an ethereal solution of the residue with 4 N isopropanolic HCl

Sources & evidence

ORD record
ord-4590362463104371aeb602494c21595d
Source dataset
uspto-grants-2006_05
Patent number
US07041683B2

Linked notes

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