Diisopropylethylamine → ethyl 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

HRID 882265Notes

Reaction equation

HRID 882265 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH2:25])[CH2:6][C@@H:5]1[CH3:26])(=[O:3])[CH3:2].Cl[C:28]1[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][N:29]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.O.CCOC(C)=O>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:24]=[CH:23][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:25][C:28]2[CH:35]=[CH:34][C:31]([C:32]#[N:33])=[CH:30][N:29]=2)[CH2:6][C@@H:5]1[CH3:26])(=[O:3])[CH3:2]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 67205707ethyl 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

Product 1

HCID 70976688ethyl 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
200 °C

Procedure

Ethyl 4-((2S,4R)-1-acetyl-4-amino-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate (for a preparation, see Intermediate 16) (300 mg, 0.851 mmol) and 6-chloronicotinonitrile (236 mg, 1.702 mmol) in anhydrous NMP (5 mL) were treated with DIPEA (0.445 mL, 2.55 mmol). The reaction vial was sealed and heated under microwave irradiation to 200° C. for 2 h. The cooled solution was diluted with water to −20 mL, stirred and the resulting sticky solid isolated by decantation. The solid was dissolved in EtOAc, the solution washed with brine and dried by passing through a hydrophobic frit. The solution was concentrated in vacuo and the residue purified by MDAP (Formate) to give crude ethyl 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate (120 mg) as a beige gum which was used directly in the next step without further purification. LCMS: (Formate, 2 min), Rt=1.12 min, MH+455.

Workup

  1. customThe reaction
  2. customvial was sealed
  3. customthe resulting sticky solid isolated by decantation
  4. washthe solution washed with brine
  5. customdried
  6. concentrationThe solution was concentrated in vacuo
  7. customthe residue purified by MDAP (Formate)

Sources & evidence

ORD record
ord-13bbddb9e35c407eadb4b2697782cb47
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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