Sodium Iodide → 6-(((2S,4R)-1-acetyl-6-(2-(2-methoxyethyl)-2H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

HRID 628958Notes

Reaction equation

HRID 628958 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:15]=[N:16][NH:17][CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:19][C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][N:21]=2)[CH2:6][C@@H:5]1[CH3:28])(=[O:3])[CH3:2].Br[CH2:30][CH2:31][O:32][CH3:33].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C=O)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:15]=[N:16][N:17]([CH2:30][CH2:31][O:32][CH3:33])[CH:18]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:19][C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][N:21]=2)[CH2:6][C@@H:5]1[CH3:28])(=[O:3])[CH3:2].[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:18]=[N:17][N:16]([CH2:30][CH2:31][O:32][CH3:33])[N:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:19][C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][N:21]=2)[CH2:6][C@@H:5]1[CH3:28])(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 5238Sodium Iodide3×HCID 11430Potassium Carbonate3×HCID 809722-Bromoethyl methyl ether3×HCID 178473712HCID 178473712, compound

Product 2

HCID 709776976-(((2S,4R)-1-acetyl-6-(2-(2-methoxyethyl)-2H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrileHCID 709781346-(((2S,4R)-1-acetyl-6-(1-(2-methoxyethyl)-1H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 6-(((2S,4R)-1-acetyl-2-methyl-6-(1H-1,2,3-triazol-4-yl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (for a preparation see Intermediate 8) (50 mg, 0.134 mmol) in DMF (3 ml) was cooled to 0° C. in an ice-water bath. To the solution was added 1-bromo-2-methoxyethane (0.04 ml, 0.420 mmol) and potassium carbonate (56 mg, 0.405 mmol). The solution was then allowed to warm to room temperature, and was stirred at ambient conditions for 2 h. Sodium iodide (61 mg, 0.407 mmol) was added to the reaction solution and the reaction was stirred at ambient temperature overnight. 1-Bromo-2-methoxyethane (0.013 ml, 0.134 mmol), potassium carbonate (21 mg, 0.152 mmol), and sodium iodide (21 mg, 0.140 mmol) were added to the reaction, which was heated at 60° C. for 1 h. Further portions of 1-bromo-2-methoxyethane (0.013 ml, 0.134 mmol), potassium carbonate (21 mg, 0.152 mmol), and sodium iodide (21 mg, 0.140 mmol) were added to the reaction and heating continued for 3 h. The reaction mixture was concentrated in vacuo, diluted with water (10 ml) and extracted with DCM (3×15 ml). The organics were combined and dried (hydrophobic frit). The solvent was then evaporated in vacuo, the sample redissolved in methanol/DMSO (1:1, 1 ml) and purified by MDAP (formate). Both regiosiomers were collected to give 6-(((2S,4R)-1-acetyl-6-(1-(2-methoxyethyl)-1H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (8 mg) and 6-(((2S,4R)-1-acetyl-6-(2-(2-methoxyethyl)-2H-1,2,3-triazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-4- yl)amino)nicotinonitrile (18 mg).

Workup

  1. temperatureto warm to room temperature
  2. stirringthe reaction was stirred at ambient temperature overnight
  3. temperaturewas heated at 60° C. for 1 h
  4. temperatureheating
  5. waitcontinued for 3 h
  6. concentrationThe reaction mixture was concentrated in vacuo
  7. additiondiluted with water (10 ml)
  8. extractionextracted with DCM (3×15 ml)
  9. customdried (hydrophobic frit)
  10. customThe solvent was then evaporated in vacuo
  11. dissolutionthe sample redissolved in methanol/DMSO (1:1, 1 ml)
  12. custompurified by MDAP (formate)
  13. customBoth regiosiomers were collected

Sources & evidence

ORD record
ord-8ddc2133be1f4f4fbbfffe0361b4b0cf
Source dataset
uspto-grants-2016_04
Patent number
US09315487B2

Reaction notes

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