Methyl iodide → HCID 69057854, compound

HRID 2105123Notes

Reaction equation

HRID 2105123 reaction equation
[CH2:1]([Li])CCC.[NH:6]([C:13]1[N:18]=[C:17]([C:19]2[N:23]3[CH2:24][CH2:25][CH2:26][CH2:27][C:22]3=[N:21][CH:20]=2)[CH:16]=[CH:15][N:14]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.IC>CCCCCC.C1COCC1>[NH:6]([C:13]1[N:18]=[C:17]([C:19]2[N:23]3[CH2:24][CH2:25][CH2:26][CH:27]([CH3:1])[C:22]3=[N:21][CH:20]=2)[CH:16]=[CH:15][N:14]=1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11403574HCID 11403574, compoundHCID 178418339Butyllithium

Product 1

HCID 69057854HCID 69057854, compoundYield 16%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

n-Butyllithium (1.2 ml of a 1.6M solution in hexane, 1.92 mmol) was added slowly to a stirred solution of 2-anilino-4-(5,6,7,8-tetrahydroimidazo[1,2-a]pyridin-3-yl)pyrimidine (Example 2; 200 mg, 0.69 mmol) in dry THF (10 ml) cooled to −78° C. under nitrogen making sure that the reaction temperature remained below −65° C. The mixture was stirred at −70° C. for 15 minutes, then iodomethane (45 μl, 0.72 mmol) was added and the reaction stirred at −70° C. for 10 minutes and then allowed to warm and stirred at ambient temperature for 20 hours. The reaction mixture was partitioned between EtOAc and water and the layers separated. The organic layer was washed with saturated brine, dried (Na2SO4) and the volatiles removed by evaporation. The residue was purified by chromatography eluting with DCM/MeOH (98:2). The purified product was twice triturated with diethyl ether, collected by filtration and dried to give the title compound (33 mg, 16%) as a pale yellow solid. NMR: 1.37 (d, 3H), 1.57 (m, 1H), 1.92 (m, 1H), 2.07 (m, 2H), 2.97 (m, 1H), 4.25 (m, 1H), 4.65 (m, 1H), 7.02 (t, 2H), 7.15 (d, 1H), 7.33 (t, 2H), 7.72 (m, 3H), 8.38 (d, 1H), 9.42 (s. 1H); m/z 306.

Workup

  1. customremained below −65° C
  2. stirringthe reaction stirred at −70° C. for 10 minutes
  3. temperatureto warm
  4. stirringstirred at ambient temperature for 20 hours
  5. customThe reaction mixture was partitioned between EtOAc and water
  6. customthe layers separated
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried (Na2SO4)
  9. customthe volatiles removed by evaporation
  10. customThe residue was purified by chromatography
  11. washeluting with DCM/MeOH (98:2)
  12. customThe purified product was twice triturated with diethyl ether
  13. filtrationcollected by filtration
  14. customdried

Sources & evidence

ORD record
ord-b293cf37fd164b46ba977e794ca29803
Source dataset
uspto-grants-2009_08
Patent number
US07579344B2

Reaction notes

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