Quinaldic Acid → HCID 58997234, compound

HRID 251126Notes

Reaction equation

HRID 251126 reaction equation
[C:1]([OH:13])(=O)[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C(Cl)(=O)C(Cl)=O.[CH3:20][C:21]1[C:22]([CH2:27][N:28]([CH2:35][C:36]2[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][N:37]=2)[CH:29]2[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)=[N:23][CH:24]=[CH:25][CH:26]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.C1COCC1.[OH-].[Na+].CCOC(C)=O.CN(C=O)C>[CH3:20][C:21]1[C:22]([CH2:27][N:28]([CH2:35][C:36]2[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][N:37]=2)[CH:29]2[CH2:34][CH2:33][N:32]([C:1]([C:2]3[CH:11]=[CH:10][C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[N:3]=3)=[O:13])[CH2:31][CH2:30]2)=[N:23][CH:24]=[CH:25][CH:26]=1

Participants

10

Reactant 4

HCID 7124Quinaldic AcidHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58997234HCID 58997234, compoundYield 60.1%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
0 °C

Procedure

To a cold (0° C.), stirred, mixture of quinaldic acid (89 mg, 0.52 mmol) in CH2Cl2 (5 mL) was added DMF (0.1 mL) followed by oxalyl chloride (0.22 mL, 2.52 mmol). The mixture was warmed to room temperature. After 15 minutes the mixture was concentrated under reduced pressure and provided a pink solid. To a solution of COMPOUND 249 (62 mg, 0.20 mmol) in THF (10 mL) was added the pink solid from above followed by DIPEA (0.50 mL, 2.87 mmol). The resultant mixture was stirred at room temperature for 2 hours then diluted with 1.0 N NaOH (10 mL) and EtOAc (30 mL). The phases were separated and the organic phase was washed with 1.0 N NaOH (3×10 mL), dried (Na2SO4), and concentrated. Purification of the crude material by radial chromatography on silica gel (1 mm plate, 50:1:1 CH2Cl2-MeOH—NH4OH) provided 56 mg (60%) of COMPOUND 267 as a yellow solid. 1H NMR (CDCl3) δ 1.73-2.03 (m, 4H), 2.10 (s, 6H), 2.64-2.86 (m, 2H), 2.97-3.05 (m, 1H), 3.79 (d, 2H, J=12.3 Hz), 3.92 (d, 2H, J=12.3 Hz), 4.09 (d, 1H, J=13.2 Hz), 4.89 (d, 1H, J=13.2 Hz), 7.09 (dd, 2H, J=7.5, 5.1 Hz), 7.37 (d, 2H, J=7.5 Hz), 7.58-7.69 (m, 2H), 7.77 (td, 1H, J=7.5, 1.2 Hz), 7.86 (d, 1H, J=7.8 Hz), 8.10 (d, 1H, J=8.4 Hz), 8.26 (d, 1H, J=8.7 Hz), 8.35 (d, 2H, J=3.6 Hz); ES-MS m/z 466 (M+H).

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. concentrationAfter 15 minutes the mixture was concentrated under reduced pressure
  3. customprovided a pink solid
  4. customThe phases were separated
  5. washthe organic phase was washed with 1.0 N NaOH (3×10 mL)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customPurification of the crude material by radial chromatography on silica gel (1 mm plate, 50:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-1e3061bc90fc4305926b1ae659b219e2
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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