8-Aminoquinoline → HCID 89813870, compound

HRID 525341Notes

Reaction equation

HRID 525341 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH:5]([C:8]([OH:10])=O)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[C:49]2[C:54]=1[N:53]=[CH:52][CH:51]=[CH:50]2>C(Cl)Cl>[O:1]=[C:2]1[CH2:3][CH2:4][CH:5]([C:8]([NH:44][C:45]2[CH:46]=[CH:47][CH:48]=[C:49]3[C:54]=2[N:53]=[CH:52][CH:51]=[CH:50]3)=[O:10])[CH2:6][CH2:7]1

Participants

6

Reactant 4

HCID 113598-AminoquinolineHCID 81531DiisopropylethylamineHCID 1927304-Oxocyclohexanecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 89813870HCID 89813870, compoundYield 50.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a flask charged with 4-oxocyclohexane carboxylic acid (commercially available from Alfa Aesar, Ward Hill, Mass.) (2.000 mL, 14.07 mmol) were added DCM (56.3 mL), DIEA (5.16 mL, 29.5 mmol), HATU (5.35 g, 14.07 mmol) and 8-aminoquinoline (commercially available from Sigma-Aldrich, Milwaukee, Wis.) (2.130 g, 14.77 mmol) respectively. The resulting light brown suspension was stirred overnight at room temperature without much color change but complete dissolution of materials. LC-MS indicated product as the primary species. The solution was dried under reduced pressure and purified ramping with EtOAc in heptane from 0-50%, then isocratic at 50% which led to the system clogging up a bit due to precipitation of product. Product eluted following a less polar impurity and the system was flushed with DCM:MeOH:NH4OH (90:10:1) to elute the remainder of the product. Solid 4-oxo-N-(quinolin-8-yl)cyclohexanecarboxamide (1.900 g, 7.08 mmol, 50.3% yield) was obtained as a tan. 1H NMR (400 MHz, CDCl3) δ=10.02 (br. s., 1H), 8.83 (dd, J=1.7, 4.2 Hz, 1H), 8.78 (dd, J=2.2, 6.7 Hz, 1H), 8.20 (dd, J=1.7, 8.3 Hz, 1H), 7.60-7.53 (m, 2H), 7.49 (dd, J=4.3, 8.3 Hz, 1H), 2.97 (tt, J=3.8, 10.5 Hz, 1H), 2.67-2.63 (m, 1H), 2.63-2.59 (m, 1H), 2.54-2.35 (m, 4H), 2.29-2.16 (m, 2H). m/z (ESI) 269.1 (M+H)+.

Workup

  1. customThe solution was dried under reduced pressure
  2. custompurified
  3. customdue to precipitation of product
  4. washProduct eluted
  5. customthe system was flushed with DCM:MeOH:NH4OH (90:10:1)
  6. washto elute the remainder of the product

Sources & evidence

ORD record
ord-c7ca707547784d80a143ac571b3b168c
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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