Hexane → 2-Anilino-4-(1-methyl-2-n-butylimidazol-5-yl)pyrimidine

HRID 2117757Notes

Reaction equation

HRID 2117757 reaction equation
[NH:1]([C:8]1[N:13]=[C:12]([C:14]2[N:18]([CH3:19])[C:17]([CH3:20])=[N:16][CH:15]=2)[CH:11]=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:21]([Li])[CH2:22][CH2:23]C.CCCCCC.C(I)CC>C1COCC1.O>[NH:1]([C:8]1[N:13]=[C:12]([C:14]2[N:18]([CH3:19])[C:17]([CH2:20][CH2:21][CH2:22][CH3:23])=[N:16][CH:15]=2)[CH:11]=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 8058Hexane2×HCID 336431-IodopropaneHCID 222734802-Anilino-4-(1,2-dimethylimidazol-5-yl)pyrimidineHCID 178418339Butyllithium2×

Product 1

HCID 693145652-Anilino-4-(1-methyl-2-n-butylimidazol-5-yl)pyrimidineYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-70 °C

Procedure

2-Anilino-4-(1,2-dimethylimidazol-5-yl)pyrimidine (Method 74; 2 g, 7.55 mmol) was dissolved in anhydrous THF (100 ml) at RT under a nitrogen atmosphere. The stirring solution was cooled using dry-ice/acetone bath to −70° C. A 1.6M solution of n-butyl lithium in hexane (6.3 ml, 10.08 mmol) was added drop-wise keeping temperature <−60° C. until the dark red colour remained. One more equivalent of n-butyl lithium in hexane (4.7 ml, 7.55 mmol), was then added dropwise keeping the temperature below −60° C. At this point the solution stirred at −70° C. for 10 minutes when propyl iodide (809 μl, 8.29 mmol) was added, the temperature was maintained at −70° C. for an additional 10 minutes then allowed to rise to RT. The reaction was allowed to stir for 1 hr at room temperature when water (100 ml) was added. The aqueous layer extracted with EtOAc (2×20 ml). Organics were combined, dried solvent evaporated in vacuo. The residue was purified by flash silica chromatography DCM:MeOH (95:5) to yield the title compound (1.03 g, 45%) as a pure white solid NMR: 0.90 (t, 3H), 1.39 (m, 2H), 1.66 (m, 2H), 2.70 (t, 2H), 3.94 (s, 3H), 6.95 (t, 1H), 7.08 (d, 1H), 7.28 (t, 2H, 7.65 (d, 2H), 7.59 (s, 1H), 8.35 (d, 1H), 9.42 (s, 1H); m/z 308.

Workup

  1. temperatureThe stirring solution was cooled
  2. customto −70° C
  3. customtemperature <−60° C.
  4. customthe temperature below −60° C
  5. additionwas added
  6. customto rise to RT
  7. additionwas added
  8. extractionThe aqueous layer extracted with EtOAc (2×20 ml)
  9. customdried solvent evaporated in vacuo
  10. customThe residue was purified by flash silica chromatography DCM:MeOH (95:5)

Sources & evidence

ORD record
ord-cfc8f39edaaf4057a79524edbc8a9e36
Source dataset
uspto-grants-2008_10
Patent number
US07442697B2

Reaction notes

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