Sodium hydride → 4-Amino-2-[1-(4-chloro-3-ethoxy-benzyl)-piperidin-4-ylamino]-pyrimidine-5-carbonitrile

HRID 2264410Notes

Reaction equation

HRID 2264410 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][CH:10]([NH2:13])[CH2:9][CH2:8]2)=[CH:4][C:3]=1[O:16][CH2:17][CH3:18].[H-].[Na+].[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[CH:26][N:25]=[C:24](Cl)[N:23]=1>CN(C=O)C>[NH2:21][C:22]1[C:27]([C:28]#[N:29])=[CH:26][N:25]=[C:24]([NH:13][CH:10]2[CH2:11][CH2:12][N:7]([CH2:6][C:5]3[CH:14]=[CH:15][C:2]([Cl:1])=[C:3]([O:16][CH2:17][CH3:18])[CH:4]=3)[CH2:8][CH2:9]2)[N:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 28011664-Amino-2-chloropyrimidine-5-carbonitrileHCID 592103771-(4-Chloro-3-ethoxybenzyl)piperidin-4-ylamine2×

Product 1

HCID 687817124-Amino-2-[1-(4-chloro-3-ethoxy-benzyl)-piperidin-4-ylamino]-pyrimidine-5-carbonitrileYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-chloro-3-ethoxy-benzyl)-piperidin-4-ylamine (40.3 mg, 0.15 mmol, 1.2 equiv; intermediate A2) 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 4-amino-2-chloro-pyrimidine-5-carbonitrile (19.3 mg, 0.125 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 17.1 mg (35%) of the title compound. MS (ISP): 387.3 [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-4eb2f88f1f124a46a552ffd60d964cbd
Source dataset
uspto-grants-2010_12
Patent number
US07855194B2

Reaction notes

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