Triethylamine → (4-(4-Chlorophenoxy)piperidin-1-yl)(8-hydroxyquinolin-2-yl)methanone

HRID 2170852Notes

Reaction equation

HRID 2170852 reaction equation
[OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([OH:14])=O)[CH:8]=[CH:7]2.[Cl:15][C:16]1[CH:28]=[CH:27][C:19]([O:20][CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)=[CH:18][CH:17]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[Cl:15][C:16]1[CH:28]=[CH:27][C:19]([O:20][CH:21]2[CH2:22][CH2:23][N:24]([C:12]([C:9]3[CH:8]=[CH:7][C:6]4[C:11](=[C:2]([OH:1])[CH:3]=[CH:4][CH:5]=4)[N:10]=3)=[O:14])[CH2:25][CH2:26]2)=[CH:18][CH:17]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 740798-Hydroxyquinaldic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 51998894-(4-Chlorophenoxy)piperidine

Product 1

HCID 67168809(4-(4-Chlorophenoxy)piperidin-1-yl)(8-hydroxyquinolin-2-yl)methanoneYield 22%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 8-hydroxyquinoline-2-carboxylic acid (15 mg, 0.079 mmol), 4-(4-chlorophenoxy)piperidine (20 mg, 0.096 mmol), and triethylamine (0.044 mL, 0.32 mmol) in DMF was added HBTU (46 mg, 0.12 mol) at room temperature. The reaction mixture was stirred at 60° C. for 2 hours. The mixture was diluted with ethyl acetate (3 mL) and washed with water (1.5 mL). The organic layer was dried over sodium sulfate, and concentrated by N2-flow. The residue was diluted with methanol and applied onto a strong cation exchange cartridge (BondElute(registered trademark) SCX, 1 g/6 mL, Varian Inc.), and the solid phase matrix was rinsed with methanol (6 mL). The crude mixture was eluted in a collection tube with 1 mol/L ammonia in methanol (6 mL) and concentrated by N2-flow. The residue was purified by preparative LC-MS to give 6.6 mg (22% yield) of the title compound.

Workup

  1. washwashed with water (1.5 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated by N2-flow
  4. additionThe residue was diluted with methanol
  5. wash), and the solid phase matrix was rinsed with methanol (6 mL)
  6. washThe crude mixture was eluted in a collection tube with 1 mol/L ammonia in methanol (6 mL)
  7. concentrationconcentrated by N2-flow
  8. customThe residue was purified by preparative LC-MS

Sources & evidence

ORD record
ord-b39fc53117904263b9816430d8f03d73
Source dataset
uspto-grants-2015_06
Patent number
US09051296B2

Reaction notes

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