Dimethylformamide → HCID 131717067, compound

HRID 973666Notes

Reaction equation

HRID 973666 reaction equation
NC1[N:3]=[C:4]([CH2:48][CH2:49][CH2:50][CH3:51])[N:5]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]3[N:28]([C:29]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)([C:36]4[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=4)[C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[N:27]=[N:26][N:25]=3)=[CH:14][CH:13]=2)C=1C(OC)=O.[H-].[Na+].[C:54]([O:57][CH2:58]C)(=[O:56])[CH3:55].[CH3:60][N:61]([CH:63]=O)[CH3:62]>CI.C(O)(=O)C>[CH2:48]([C:4]1[N:5]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:24]3[N:28]([C:29]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)[C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[N:27]=[N:26][N:25]=3)=[CH:16][CH:17]=2)[C:55]([C:54]([O:57][CH3:58])=[O:56])=[C:63]([N:61]([CH3:62])[CH3:60])[N:3]=1)[CH2:49][CH2:50][CH3:51]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 131717066HCID 131717066, compound

Product 1

HCID 131717067HCID 131717067, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6328Methyl iodideCatalyst

Procedure

To a solution of 103 mg (0.15 mmol) 2-butyl-4-amino-5-carbomethoxy-1-(2'-(N-triphenylmethyltetra-zol-5-yl)-biphen-4-yl)methylimidazole (Example 1, Step I) in 1 mL dry DMF at room temperature was added 7 mg sodium hydride/oil dispersion (60% dispersion; 0.18 mmol, 1.1 eq). After 15 minutes at room temperature, two drops of methyl iodide were added and the mixture capped tightly and stirred at room temperature for 16 hours. Two drops of glacial acetic acid were added and the mixture diluted into 20 mL ethyl acetate and washed with pH 7.0 phosphate buffer (2×) and brine (1×). The organic layer was removed, dried over magnesium sulfate, filtered and stripped; the residue was purified by medium pressure liquid chromatography on silica, eluting with ethyl acetate/hexane (2:1) to afford 65 mg of a 2:1 mixture of mono- and di-methylated products in addition to 23 mg of recovered starting material.

Workup

  1. customthe mixture capped tightly
  2. washwashed with pH 7.0 phosphate buffer (2×) and brine (1×)
  3. customThe organic layer was removed
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customthe residue was purified by medium pressure liquid chromatography on silica
  7. washeluting with ethyl acetate/hexane (2:1)
  8. customto afford
  9. addition65 mg of a 2:1 mixture of mono- and di-methylated products
  10. additionin addition to 23 mg
  11. customof recovered

Sources & evidence

ORD record
ord-93c7aad5a07e49268cad92fdc7be9733
Source dataset
uspto-grants-1991_11
Patent number
US05064825

Reaction notes

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