Methyl iodide → HCID 10296090, compound

HRID 1168197Notes

Reaction equation

HRID 1168197 reaction equation
[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[N:12][C:13]3[C:18]([C:19]=2[OH:20])=[CH:17][C:16]([CH2:21][N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:15][CH:14]=3)=[O:9])=[CH:4][CH:3]=1.[CH3:30][Si]([N-][Si](C)(C)C)(C)C.[Li+].CI>CS(C)=O>[Cl:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH2:21][N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)[CH:17]=3)[N:12]([CH3:30])[N:11]=2)=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 178522948HCID 178522948, compound

Product 1

HCID 10296090HCID 10296090, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a suspension of N-(4-chlorobenzyl)-4-hydroxy-6-(4-morpholinylmethyl)-3-cinnolinecarboxamide [Preparation 12] (200 mg) in dry DMSO (15 mL) is added lithium bis(trimethylsilyl)amide (0.51 mL of a 1 M solution in hexanes). The mixture is stirred for 15 min over which time everything dissolves. Methyl iodide (0.032 mL) is then added and the reaction is stirred for an additional 2 h. The mixture is partitioned between EtOAc and water. The aqueous layer is extracted with EtOAc (3×). The combined organic layers are washed with brine, dried and condensed. The crude product is chromatographed on silica (gradient CH2Cl2, 1% MeOH/CH2Cl2, 2% MeOH/CH2Cl2, 3% MeOH/CH2Cl2). Fractions homogeneous by TLC are combined and concentrated. The residue from the column is dissolved in CH2Cl2. Hexanes are added to precipitate the product. The resulting solid is collected and dried to yield 0.079 g (39%) of the title compound as a white solid. Physical characteristics are the same as reported above.

Workup

  1. dissolutiondissolves
  2. stirringthe reaction is stirred for an additional 2 h
  3. customThe mixture is partitioned between EtOAc and water
  4. extractionThe aqueous layer is extracted with EtOAc (3×)
  5. washThe combined organic layers are washed with brine
  6. customdried
  7. customcondensed
  8. customThe crude product is chromatographed on silica (gradient CH2Cl2, 1% MeOH/CH2Cl2, 2% MeOH/CH2Cl2, 3% MeOH/CH2Cl2)
  9. concentrationconcentrated
  10. dissolutionThe residue from the column is dissolved in CH2Cl2
  11. additionHexanes are added
  12. customto precipitate the product
  13. customThe resulting solid is collected
  14. customdried

Sources & evidence

ORD record
ord-b59f2b2109534781bf2904407c246ea6
Source dataset
uspto-grants-2003_09
Patent number
US06624160B2

Reaction notes

Loading…