Sodium hydride → HCID 68781541, compound

HRID 2264393Notes

Reaction equation

HRID 2264393 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+].[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[CH:27][N:26]=[C:25](Cl)[N:24]=1>CN(C=O)C>[NH2:22][C:23]1[C:28]([C:29]#[N:30])=[CH:27][N:26]=[C:25]([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:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 28011664-Amino-2-chloropyrimidine-5-carbonitrileHCID 392574451-(3-Ethoxy-4-methoxy-benzyl)-piperidin-4-ylamine2×

Product 1

HCID 68781541HCID 68781541, compoundYield 34%

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, 1.5 equiv; intermediate A1) in dry DMF (1.5 mL) under Ar was added sodium hydride (6.6 mg, 0.15 mmol, 1.5 equiv; 55% free-flowing powder moistened with oil) and the reaction mixture stirred at rt. After 2 h 4-amino-2-chloro-pyrimidine-5-carbonitrile (15.5 mg, 0.10 mmol, 1.0 equiv; commercially available) was added and the mixture heated by microwave irradiation to 140° C. for 1 h. Removal of the solvent under reduced pressure and purification by preparative HPLC on reversed phase eluting with a gradient of acetonitrile/water provided 19.7 mg (34%) of the title compound. MS (ISP): 383.4 [M+H]+.

Workup

  1. additioncommercially available) was added
  2. temperaturethe mixture heated by microwave irradiation to 140° C. for 1 h
  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-c02034a86d7b4385b802e93ef295c07d
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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