Water → 6-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

HRID 628948

Reaction equation

HRID 628948 reaction equation
[NH2:1][C@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Br:12])[CH:10]=2)[N:5]([C:13](=[O:15])[CH3:14])[C@@H:4]([CH3:16])[CH2:3]1.Cl[C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][N:19]=1.CCN(C(C)C)C(C)C.O>CN1C(=O)CCC1>[C:13]([N:5]1[C:6]2[C:11](=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=2)[C@H:2]([NH:1][C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][N:19]=2)[CH2:3][C@@H:4]1[CH3:16])(=[O:15])[CH3:14]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 67194540HCID 67194540, compound

Product 1

HCID 709779596-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrileYield 76%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

1-((2S,4R)-4-amino-6-bromo-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation, see Intermediate 7) (18 g, 63.6 mmol) was dissolved in dry NMP (90 mL). 6-chloronicotinonitrile (13.21 g, 95 mmol) and DIPEA (22.20 ml, 127 mmol) were added, the mixture was stirred at 150° C. under a nitrogen atmosphere for 8 h, then allowed to stand overnight at room temperature. The solution was added to water (1 L) and the mixture extracted with EtOAc (2×400 mL). The organic layer was washed with water (2×500 mL), dried and evaporated in vacuo to give a brown foam. This brown foam was purified by silica gel column chromatography (750 g column, eluting with 0-100% EtOAc/cyclohexane). The appropriate fractions were combined and evaporated in vacuo to give 6-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (18.7 g, 48.5 mmol, 76% yield) as a pale yellow solid.

Workup

  1. waitto stand overnight at room temperature
  2. extractionthe mixture extracted with EtOAc (2×400 mL)
  3. washThe organic layer was washed with water (2×500 mL)
  4. customdried
  5. customevaporated in vacuo
  6. customto give a brown foam
  7. customThis brown foam was purified by silica gel column chromatography (750 g column, eluting with 0-100% EtOAc/cyclohexane)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-fe3e71d5a9a34879b96ca9b7fd53c79c
Source dataset
uspto-grants-2016_04
Patent number
US09315487B2

Linked notes

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