Sodium hydride → HCID 24855075, compound

HRID 913079Notes

Reaction equation

HRID 913079 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:15]=[CH:16][C:17]=1[O:18][CH3:19])[CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)[CH3:2].[H-].[Na+].[CH2:22]([O:24][C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29](Cl)=[N:28][CH:27]=1)[CH3:23]>CN(C=O)C>[CH2:22]([O:24][C:25](=[O:33])[C:26]1[CH:31]=[CH:30][C:29]([NH:14][CH:11]2[CH2:10][CH2:9][N:8]([CH2:7][C:6]3[CH:15]=[CH:16][C:17]([O:18][CH3:19])=[C:4]([O:3][CH2:1][CH3:2])[CH:5]=3)[CH2:13][CH2:12]2)=[N:28][CH:27]=1)[CH3:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2799611Ethyl 6-chloronicotinateHCID 392574451-(3-Ethoxy-4-methoxy-benzyl)-piperidin-4-ylamine2×

Product 1

HCID 24855075HCID 24855075, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(3-ethoxy-4-methoxy-benzyl)-piperidin-4-ylamine (39.7 mg, 0.15 mmol, 1.0 equiv; intermediate A1) in dry DMF (1.5 mL) under Ar was added sodium hydride (6.6 mg, 0.15 mmol, 1.0 equiv; 55% free-flowing powder moistened with oil) and the reaction mixture stirred at rt. After 2 h, 6-chloro-nicotinic acid ethyl ester (46.4 mg, 0.25 mmol, 1.67 equiv; commercially available) was added and the mixture heated by microwave irradiation to 220° C. for 15 min. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 10.9 mg (18%) of the title compound. MS (ISP): 414.4 [M+H]+.

Workup

  1. additioncommercially available) was added
  2. temperaturethe mixture heated by microwave irradiation to 220° C. for 15 min
  3. customRemoval of the solvent
  4. customunder reduced pressure and purification by preparative HPLC on reversed phase
  5. washeluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-0fcdd51212464ee2bcbb57ef03bcb006
Source dataset
uspto-grants-2011_09
Patent number
US08026255B2

Reaction notes

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