Methyl bromoacetate → HCID 68866136, compound

HRID 494134Notes

Reaction equation

HRID 494134 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][C:29]=1[F:30])[CH2:5][N:6]1[C:11](=[O:12])[C:10]2[C:13]([O:22][CH3:23])=[C:14]3[C:19](=[O:20])[N:18]([CH3:21])[CH2:17][CH2:16][N:15]3[C:9]=2[C:8]([CH2:24][C:25]#[N:26])=[N:7]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:42][C:43]([O:45][CH3:46])=[O:44]>CN(C=O)C.C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][C:29]=1[F:30])[CH2:5][N:6]1[C:11](=[O:12])[C:10]2[C:13]([O:22][CH3:23])=[C:14]3[C:19](=[O:20])[N:18]([CH3:21])[CH2:17][CH2:16][N:15]3[C:9]=2[C:8]([CH:24]([C:25]#[N:26])[CH2:42][C:43]([O:45][CH3:46])=[O:44])=[N:7]1

Participants

6

Reactant 3

HCID 60984Methyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 68867663HCID 68867663, compound

Product 1

HCID 68866136HCID 68866136, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a cold (0° C.) solution of 2-(3-chloro-4-fluorobenzyl)-4-(cyanomethyl)-10-methoxy-8-methyl-7,8-dihydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione (0.11 g, 0.25 mmol; Example 118, step 1) in anhydrous DMF (1 mL), a solution of lithium bis(trimethylsilyl)amide (0.28 mL, 0.28 mmol; 1M) in THF was added over a period of 5 minutes. The reaction solution was stirred at the same temperature for 30 minutes and treated with methyl bromoacetate (43 mg, 0.28 mmol). After stirring at room temperature for two hours, the product mixture was concentrated under vacuum. The residue was partitioned between dichloromethane and aqueous ammonium chloride. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 0 to 10% methanol in chloroform gradient. Collection and concentration of appropriate fractions afforded the title compound.

Workup

  1. stirringAfter stirring at room temperature for two hours
  2. concentrationthe product mixture was concentrated under vacuum
  3. customThe residue was partitioned between dichloromethane and aqueous ammonium chloride
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-3d41865ce1dd49a3bb13cc72bf24f30a
Source dataset
uspto-grants-2009_05
Patent number
US07538112B2

Reaction notes

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