Oxalyl chloride → HCID 58997148, compound

HRID 251127Notes

Reaction equation

HRID 251127 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([OH:13])=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=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:11]([C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][CH:8]=3)[N:1]=[CH:2][CH:3]=[CH:4]4)=[O:13])[CH2:31][CH2:30]2)=[N:23][CH:24]=[CH:25][CH:26]=1

Participants

10

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 825716-Quinolinecarboxylic acidHCID 58996965Bis-(3-methyl-pyridin-2-ylmethyl)-piperidin-4-yl-amine

Product 1

HCID 58997148HCID 58997148, compoundYield 29.3%

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 6-quinoline carboxylic acid (101 mg, 0.59 mmol) in CH2Cl2 (5 mL) was added DMF (0.5 mL) followed by oxalyl chloride (0.25 mL, 2.87 mmol). The mixture was warmed to room temperature. After 15 minutes the mixture was concentrated under reduced pressure and provided a white solid. To a solution of COMPOUND 249 (68 mg, 0.22 mmol) in THF (10 mL) was added the white solid from above followed by DIPEA (0.60 mL, 3.44 mmol). The resultant mixture was stirred at room temperature for 2.5 hours then diluted with 1.0 N NaOH (10 mL) and EtOAc (40 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 column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) followed by radial chromatography on silica gel (1 mm plate, 100:1:1 CH2Cl2-MeOH—NH4OH) provided 30 mg (29%) of COMPOUND 268 as a yellow solid. 1H NMR (CDCl3) δ 1.65-2.03 (m, 4H), 2.10 (s, 6H), 2.64-3.05 (m, 3H), 3.66-3.90 (m, 5H), 4.80-4.88 (m, 1H), 7.10 (dd, 2H, J=7.5, 4.8 Hz), 7.38 (d, 2H, J=7.5 Hz), 7.46 (dd, 1H, J=8.4, 4.2 Hz), 7.72 (dd, 1H, J=8.4, 1.5 Hz), 7.90 (s, 1H), 8.13-8.21 (m, 2H), 8.35 (d, 2H, J=3.6 Hz), 8.97 (d, 1H, 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 white 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 column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH)

Sources & evidence

ORD record
ord-135546ad150c4186a84b4a4e13f9529e
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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