Potassium Iodide → HCID 18617507, compound

HRID 1264249Notes

Reaction equation

HRID 1264249 reaction equation
[CH3:1][N:2]([CH3:23])[CH2:3][CH2:4][N:5]1[C:10](=[O:11])[CH:9]=[CH:8][C:7]([C:12]2[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][CH:13]=2)=[CH:6]1.[O:24]=[C:25]1[NH:30][CH:29]=[C:28]([C:31]2[CH:41]=[CH:40][C:34]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:33][CH:32]=2)[CH:27]=[CH:26]1.[H-].[Na+].[I-].[K+].Cl.[CH3:47][N:48]([CH3:52])[CH2:49][CH2:50]Cl.C(O)(C(F)(F)F)=O>C1COCC1.CN(C=O)C>[CH3:23][N:2]([CH3:1])[CH2:3][CH2:4][N:5]1[C:10](=[O:11])[CH:9]=[CH:8][C:7]([C:12]2[CH:13]=[CH:14][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:21][CH:22]=2)=[CH:6]1.[CH3:47][N:48]([CH3:52])[CH2:49][CH2:50][O:24][C:25]1[N:30]=[CH:29][C:28]([C:31]2[CH:41]=[CH:40][C:34]([C:35]([O:37][CH2:38][CH3:39])=[O:36])=[CH:33][CH:32]=2)=[CH:27][CH:26]=1

Participants

10

Reactant 6

HCID 4875Potassium IodideHCID 6422Trifluoroacetic acidHCID 24758Sodium hydrideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 18617507HCID 18617507, compoundHCID 18617564Ethyl 4-(6-oxo-1,6-dihydropyridin-3-yl)benzoate

Product 2

HCID 18617474HCID 18617474, compoundYield 12.5%HCID 18617507HCID 18617507, compoundYield 38.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

Ethyl 4-(1-[2-dimethylaminoethyl]-6-oxo-1,6-dihydropyridin-3-yl)benzoate and Ethyl 4-(6-[2-dimethyl-aminoethoxy]pyridin-3-yl)benzoate. To a cooled (0° C.) slurry of ethyl 4-(6-oxo-1,6-dihydropyridin-3-yl)benzoate [0.500 g, 2.06 mmol, reference example 36f] in THF:DMF [30 mL 5:1] is added 60% sodium hydride [0.247 g, 6.18 mmol]. After ten minutes added potassium iodide [2 mg] and 2-dimethylaminoethyl-chloride hydrochloride [Aldrich, 0.386 g, 2.68 mmol] and heated to 50° C. After twenty hours, quenched slowly with H2O [15 ml] and extracted with CH2Cl2. The organic extracts are combined and concentrated, then purified on an HPLC (40 to 60% AcCN in water with 0.1% TFA) to give ethyl 4-(1-[2-dimethylamino-ethyl]-6-oxo-1,6-dihydropyridin-3-yl)benzoate [0.337 g, 38.2% yield] as the TFA salt and ethyl 4-(6-[2-di-methylaminoethoxy]pyridin-3-yl)benzoate [0.110 g, 12.5%] yield as the TFA salt. For ethyl 4-(1-[2-dimethylaminoethyl]-6-oxo-1,6-dihydropyridin-3-yl)benzoate: 1H NMR (CD3OD): δ 1.40 (3H, t, J=7.8 Hz), 3.03 (6H, s), 3.62 (2H, t, J=5.9 Hz), 4.38 (2H, q, J=7.8 Hz), 4.49 (2H, t, J=5.9 Hz), 6.72 (1H, d, J=9.2 Hz), 7.68 (2H, d, J=8.8 Hz), 7.98 (1H, dd, J=9.2 Hz, 3.0 Hz), 8.07 (2H, d, J=8.8 Hz), 8.13 (1H, d, J=3.0 Hz). MS (ion spray) m/z 315 (M+H)+. For ethyl 4-(6-[2-dimethylaminoethoxy]pyridin-3-yl)benzoate: 1H NMR (CD3OD): δ 1.41 (3H, t, J=8.1 Hz), 3.02 (6H, s), 3.64 (2H, t, J=6.1 Hz), 4.39 (2H, q, J=8.1 Hz), 4.74 (2H, t, J=6.1 Hz), 7.01 (1H, d, J=9.4 Hz), 7.73 (2H, d, J=8.8 Hz), 8.07 (1H, dd, J=9.4 Hz, 2.5 Hz), 8.10 (2H, d, J=8.8 Hz), 8.51 (1H, d, J=2.5 Hz). MS (ion spray) m/z 315 (M+H)+.

Workup

  1. waitAfter twenty hours
  2. customquenched slowly with H2O [15 ml]
  3. extractionextracted with CH2Cl2
  4. concentrationconcentrated
  5. custompurified on an HPLC (40 to 60% AcCN in water with 0.1% TFA)

Sources & evidence

ORD record
ord-18dc6c0fcaee47ca900c6b4f80ea4f9d
Source dataset
uspto-grants-2003_04
Patent number
US06541505B1

Reaction notes

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