Acetic Acid → 2-(N-(2-bromo-4-(2-propyl)phenyl)-N-ethylamino)-4-(morpholinomethyl)-6-methylpyrimidine

HRID 1872035Notes

Reaction equation

HRID 1872035 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:27][CH3:28])[C:12]1[N:17]=[C:16]([CH3:18])[CH:15]=[C:14]([C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=O)[N:13]=1.B.C(O)(=O)C.[OH-].[Na+]>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([CH2:27][CH3:28])[C:12]1[N:13]=[C:14]([CH2:19][N:21]2[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)[CH:15]=[C:16]([CH3:18])[N:17]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6331BoraneHCID 14798Sodium HydroxideHCID 15490843N-(2-Bromo-4-(1-Methylethyl)Phenyl)-N-Ethyl-4-Methyl-6-(4-Morpholinylcarbonyl)-2-Pyrimidinamine

Product 1

HCID 102522822-(N-(2-bromo-4-(2-propyl)phenyl)-N-ethylamino)-4-(morpholinomethyl)-6-methylpyrimidineYield 40.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-methyl-6-(4-morpholinylcarbonyl)-2-pyrimidinamine (750 mg, 1.72 mmol) in anhydrous THF (1.4 mL) was stirred at ambient temperature under a nitrogen atmosphere. A solution of borane in THF (1 M, 3.6 mL, 3.6 mmol) was added dropwise. The reaction mixture was then warmed to reflux temperature and stirred for 20 hours. After cooling to room temperature, acetic acid (3.5 mL) was added slowly and the mixture was heated to reflux temperature and stirred for 30 min. After being cooled to ambient temperature, the reaction mixture was poured onto a 3 N NaOH solution, mixed and extracted three times with EtOAc. The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. Column chromatography (EtOAc) of the residue afforded the title compound as an oil (300 mg, 39% yield, Rf 0.3): NMR (CDCl3, 300 MHz): d 7.5 (s, 1H), 7.2 (d, 1H, J=7), 7.15 (d, 1H, J=7), 6.5 (s, 1H), 4.3-4.1 (m, 1H), 3.8-3.6 (m, 7H), 3.5-3.3 (m, 2H), 2.9 (septet, 1H, J=7), 2.55-2.35 (br m, 3H), 2.35-2.25 (m, 2H), 1.3 (d, 6H, J=7), 1.2 (t, 3H, J=7); CI-HRMS: calcd: 4.33.1603 (M+H), found: 433.1586.

Workup

  1. temperatureThe reaction mixture was then warmed
  2. temperatureto reflux temperature
  3. temperaturethe mixture was heated
  4. temperatureto reflux temperature
  5. stirringstirred for 30 min
  6. temperatureAfter being cooled to ambient temperature
  7. additionmixed
  8. extractionextracted three times with EtOAc
  9. dry with materialThe combined organic layers were dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f4cffd6c8c594c38829c35f5a7fc82cb
Source dataset
uspto-grants-2000_08
Patent number
US06107301

Reaction notes

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