Methyl iodide → HCID 178430022, compound

HRID 1371205Notes

Reaction equation

HRID 1371205 reaction equation
Cl.[CH3:2][C:3]1[CH:4]=[N:5][C:6]2[C:7]=1[NH:8][C:9]([CH:12]1[CH2:17][CH:16]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[NH:15][CH2:14][CH2:13]1)=[N:10][CH:11]=2.[Li+].[CH3:25][Si]([N-][Si](C)(C)C)(C)C.CI>C1COCC1>[CH3:25][CH:17]1[CH:16]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[NH:15][CH2:14][CH2:13][CH:12]1[C:9]1[NH:8][C:7]2=[C:3]([CH3:2])[CH:4]=[N:5][C:6]2=[CH:11][N:10]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 178430024HCID 178430024, compound

Product 1

HCID 178430022HCID 178430022, compoundYield 87.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 7-methyl-6-phenyl-4-piperidylpyrrolo[3,2-d]pyrimidine (Example 89) (177.3 mg, 0.61 mmol) in THF (10 mL) under a nitrogen atmosphere was added LiHMDS (1.0 M soln from Aldrich Chemical Company) (1.3 mL, 1.27 mmol). This mixture was stirred at 0° C. for 0.5 h then CH3I (Aldrich Chemical Comapny) (41 mL, 0.67 mmol) was added. The 0° C. bath was removed and the solution stirred at room temperature for 2.5 h. The reaction mixture was poured into a separatory funnel containing EtOAc (35 mL) and H2O (50 mL). The organic solution was collected washed with H2O (3×40 mL), saturated NaCl (70 mL), dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified via flash chromatography on silica gel 95:5 CHCl3/MeOH as eluant to give 164 mg (86%) of the title compound as a beige colored solid. Mp: 123.0-125.0° C. 1H NMR (DMSO-d6; 400 MHz): δ 1.68 (m, 2), 1.78 (m, 4), 2.30 (s, 3), 3.42 (br s, 4), 3.66 (s, 3), 7.44-7.54 (m, 5), 8.61 (s, 1) MS m/z: 307 (M+1).

Workup

  1. customThe 0° C. bath was removed
  2. stirringthe solution stirred at room temperature for 2.5 h
  3. additionThe reaction mixture was poured into a separatory funnel
  4. additioncontaining EtOAc (35 mL) and H2O (50 mL)
  5. customThe organic solution was collected
  6. washwashed with H2O (3×40 mL), saturated NaCl (70 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified via flash chromatography on silica gel 95:5 CHCl3/MeOH as eluant

Sources & evidence

ORD record
ord-60964eed72964074b4527819896b6652
Source dataset
uspto-grants-2003_06
Patent number
US06583154B1

Reaction notes

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