Morpholine → N-(2-Bromo-4-(1-Methylethyl)Phenyl)-N-Ethyl-4-Methyl-6-(4-Morpholinylcarbonyl)-2-Pyrimidinamine

HRID 1872034Notes

Reaction equation

HRID 1872034 reaction equation
[H-].[Na+].[NH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[Br:9][C:10]1[CH:15]=[C:14]([CH:16]([CH3:18])[CH3:17])[CH:13]=[CH:12][C:11]=1[N:19]([C:22]1[N:27]=[C:26]([C:28](OC)=[O:29])[CH:25]=[C:24]([CH3:32])[N:23]=1)[CH2:20][CH3:21].[OH-].[Na+]>C1COCC1.CCOCC>[Br:9][C:10]1[CH:15]=[C:14]([CH:16]([CH3:17])[CH3:18])[CH:13]=[CH:12][C:11]=1[N:19]([CH2:20][CH3:21])[C:22]1[N:23]=[C:24]([CH3:32])[CH:25]=[C:26]([C:28]([N:3]2[CH2:8][CH2:7][O:6][CH2:5][CH2:4]2)=[O:29])[N:27]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 183237072-(N-(2-bromo-4-(2-propyl)phenyl)-N-ethylamino)-4-carbomethoxy-6-methyl-pyrimidine

Product 1

HCID 15490843N-(2-Bromo-4-(1-Methylethyl)Phenyl)-N-Ethyl-4-Methyl-6-(4-Morpholinylcarbonyl)-2-PyrimidinamineYield 39.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To sodium hydride (60% in oil, 0.24 g, 6.0 mmol) suspended in anhydrous THF (10 mL) was added morpholine (0.52 g, 6.0 mmol) with stirring; the reaction mixture was warmed to reflux temperature and stirred for 1 hour. The reaction mixture was then cooled to ambient temperature and 2-(N-(2-bromo-4-(2-propyl)-phenyl)-N-ethylamino)-4-carbomethoxy-6-methyl-pyrimidine (2.0 g, 5.1 mmol) was added. Stirring was continued for 26 hours. The reaction mixture was then poured onto a 1 N NaOH solution, stirred and extracted three time with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. Column chromatography (Et2O) afforded the title compound as a solid (900 mg, 39% yield): mp 145° C.; NMR (CDCl3, 300 MHz): d 7.5 (d, 1H, J=1), 7.2 (dd, 1H, J=7.1), 7.1 (d, 1H, J=7), 6.8 (br s, 1H), 4.3-4.15 (m, 1H), 3.9-3.3 (m, 11H), 3.1-3.0 (m, 1H), 2.9 (septet, 1H, J=7), 1.3 (d, 6H, J=7), 1.15 (t, 3H, J=7); Anal. (C21H27BrN4O2) Calcd: C, 56.38, H, 6.08, N, 12.52, Br, 17.86; Found: C, 56.07, H, 6.05, N, 12.29, Br, 18.08.

Workup

  1. temperaturethe reaction mixture was warmed
  2. temperatureto reflux temperature
  3. stirringstirred for 1 hour
  4. stirringStirring
  5. stirringstirred
  6. extractionextracted three time with EtOAc
  7. dry with materialThe combined organic layers were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b382e7388c5c4c96bf42f8a18f5e9d2f
Source dataset
uspto-grants-2000_08
Patent number
US06107301

Reaction notes

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