Sodium hydride → HCID 24855026, compound

HRID 913077Notes

Reaction equation

HRID 913077 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+].Cl[C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][N:24]=1>CN(C=O)C>[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[CH2:9][CH2:10][CH:11]([NH:14][C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][N:24]=2)[CH2:12][CH2:13]1)[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 392574451-(3-Ethoxy-4-methoxy-benzyl)-piperidin-4-ylamine2×

Product 1

HCID 24855026HCID 24855026, compoundYield 8%

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, 1.2 equiv; intermediate A1) in dry DMF (1.5 mL) under Ar was added sodium hydride (6.6 mg, 0.15 mmol, 1.2 equiv; 55% free-flowing powder moistened with oil) and the reaction mixture stirred at rt. After 2 h, 2-chloro-5-trifluoromethyl-pyridine (22.7 mg, 0.125 mmol, 1.0 equiv; commercially available) was added and the mixture heated by microwave irradiation to 160° 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 4.8 mg (8%) of the title compound. MS (ISP): 410.3 [M+H]+.

Workup

  1. additioncommercially available) was added
  2. temperaturethe mixture heated by microwave irradiation to 160° 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-db53b52edd85429388ab9960226c4b68
Source dataset
uspto-grants-2011_09
Patent number
US08026255B2

Reaction notes

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