Methyl iodide → HCID 54435985, compound

HRID 1432935Notes

Reaction equation

HRID 1432935 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][NH:16][C:17]2[C:22](Cl)=[C:21](Cl)[N:20]=[C:19](Cl)[C:18]=2Cl)[C:10](=[O:27])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:30]I.C[O-].[Na+].[H][H]>CN(C=O)C.CCOC(C)=O.CO.[Pd]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]([CH3:30])[C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)[C:10](=[O:27])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

10

Reactant 5

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10942334Sodium MethoxideHCID 54436285HCID 54436285, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 54435985HCID 54435985, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(tert-Butyloxycarbonyl)-1-[2-(2,3,5,6-tetrachloropyridin-4-ylamino)-ethyl]-piperazin-2-one (0.19 g, 0.41 mmol), Example 92, Part B, is dissolved in DMF (3 ml) and treated with 60% NaH (20 mg, 0.5 mmol). After 10 minutes methyl iodide (0.025 ml, 0.40 mmol) is added and the yellow solution is stirred at r.t. overnight. The solution is diluted with EtOAc and washed with H2O (6×). The organic layer is dried (MgSO4) and concentrated to a residue (0.19 g, 0.40 mmol). The residue is dissolved in methanol (2 ml) and treated with 0.5 M NaOMe in MeOH (8 ml, 4.0 mmol)). The solution is treated with Pd/C and agitated under 60 PSI of hydrogen gas overnight and filtered. The filtrate is concentrated and extracted several times with CH2Cl2; removal of solvent in vacuo gives 4-(tert-Butyloxycarbonyl)-1-[2-{(methyl)-(pyridin-4-yl)-amino}-ethyl]-piperazin-2-one as an amorphous residue (0.16 g). EI MS m/z: 335, [M+1]+; 1H NMR (CDCl3, 300 MHz) δ8.21 (d, 2H), 6.56 (d, 2H), 3.99 (s, 2H), 3.60 (t, 2H), 3.53 (t, 2H), 3.47 (t, 2H), 3.28 (t, 2H), 2.98 (s, 3H), 1.46 (s, 9H). Treatment of the above product with 20% TFA/CH2Cl2 (10 mL) at r.t. for 1 h gives, after concentration, the title compound as a residue which is used without further purification. 1H NMR (CD3OD, 300 MHz) δ8.14 (d, 2H), 7.30 (br, 1H), 7.00 (br, 1H), 3.88-3.67 (m, 8H), 3.53 (t, 2H), 2.26 (s, 3H).

Workup

  1. washwashed with H2O (6×)
  2. dry with materialThe organic layer is dried (MgSO4)
  3. filtrationfiltered
  4. concentrationThe filtrate is concentrated
  5. extractionextracted several times with CH2Cl2
  6. customremoval of solvent in vacuo

Sources & evidence

ORD record
ord-b2082178e2ed4af286b44b00f6d0c316
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

Loading…