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

HRID 1251510Notes

Reaction equation

HRID 1251510 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]([C:14]1[N:19]=[C:18](C(O)=O)[CH:17]=[C:16]([CH3:23])[N:15]=1)[CH2:12][CH3:13].[N:24]1([C:30](N)=O)[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.B.[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C.C(O)(=O)C>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[N:11]([C:14]1[N:19]=[C:18]([CH2:30][N:24]2[CH2:25][CH2:26][O:27][CH2:28][CH2:29]2)[CH:17]=[C:16]([CH3:23])[N:15]=1)[CH2:12][CH3:13]

Participants

8

Reactant 4

HCID 6331BoraneHCID 14798Sodium HydroxideHCID 75088Morpholine-4-carboxamideHCID 18323680N-(2-bromo-4-(1-methylethyl)phenyl)-N-ethyl-4-carboxy-6-methylpyrimidinamine

Product 1

HCID 102522822-(N-(2-bromo-4-(2-propyl)phenyl)-N-ethylamino)-4-(morpholinomethyl)-6-methylpyrimidineYield 39%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(N-(2-bromo-4-(2-propyl)phenyl)-N-ethylamino)-6-methylpyrimidine-4-carboxylic acid, morpholine amide (750 mg, 1.72 mmol) in anhydrous tetrahydrofuran (1.4 mL) at ambient temperature under a nitrogen atmosphere was added a solution of borane in tetrahydrofuran (1 M, 3.6 mL, 3.6 mmol) dropwise and the reaction mixture was heated at reflux temperature for 20 h. After cooling to room, acetic acid (3.5 mL) was slowly added and the mixture was heated at reflux for 30 min. After being cooled to ambient temperature, the reaction mixture was poured into a 3 N NaOH solution and extracted three times with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. Column chromatography (ethyl acetate) afforded the title compound as an oil (300 mg, 39% yield, Rf 0.3): NMR (CDCl3, 300 MHz) 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: 433.1603 (M+H), found: 433.1586.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux temperature for 20 h
  3. additionwas slowly added
  4. temperaturethe mixture was heated
  5. temperatureat reflux for 30 min
  6. extractionextracted three times with ethyl acetate
  7. dry with materialThe combined organic layers were dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b20d2d3e373a41d5929f7a6bf788d7f2
Source dataset
uspto-grants-2002_01
Patent number
US06342503B1

Reaction notes

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