Tetrabutylammonium Fluoride → 6-(((2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

HRID 628952Notes

Reaction equation

HRID 628952 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]#[C:15][Si](C)(C)C)=[CH:11][CH:12]=2)[C@H:7]([NH:20][C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=2)[CH2:6][C@@H:5]1[CH3:29])(=[O:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]#[CH:15])=[CH:11][CH:12]=2)[C@H:7]([NH:20][C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][N:22]=2)[CH2:6][C@@H:5]1[CH3:29])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 709781736-(((2S,4R)-1-Acetyl-2-methyl-6-((trimethylsilyl)ethynyl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

Product 1

HCID 867120316-(((2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

6-(((2S,4R)-1-Acetyl-2-methyl-6-((trimethylsilyl)ethynyl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (for a preparation see Intermediate 10) (1.69 g, 4.20 mmol) was treated with tetrabutylammonium fluoride (1M in THF, 4.62 ml, 4.62 mmol) and THF (18 ml) and the solution stirred at ambient conditions for 30 min. The reaction was concentrated in vacuo, diluted with water (25 ml) and extracted with DCM (3×30 ml). The organics were combined, being dried (hydrophobic frit) and the solvent evaporated in vacuo. The residue was purified by chromatography on a silica cartridge (100 g) eluting with an ethyl acetate/cyclohexane gradient (0-75%). The appropriate fractions were collected and the solvent evaporated in vacuo to give 6-(((2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (990 mg) as a yellow foam. LCMS (formate), Rt 0.92 min, MH+ 331.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. additiondiluted with water (25 ml)
  3. extractionextracted with DCM (3×30 ml)
  4. custombeing dried (hydrophobic frit)
  5. customthe solvent evaporated in vacuo
  6. customThe residue was purified by chromatography on a silica cartridge (100 g)
  7. washeluting with an ethyl acetate/cyclohexane gradient (0-75%)
  8. customThe appropriate fractions were collected
  9. customthe solvent evaporated in vacuo

Sources & evidence

ORD record
ord-43f9a16c5b5a45bab8035f16c9c84b89
Source dataset
uspto-grants-2016_04
Patent number
US09315487B2

Reaction notes

Loading…