Lithium Hexamethyldisilazide → HCID 68865408, compound

HRID 494119Notes

Reaction equation

HRID 494119 reaction equation
[CH2:1]([N:3]1[CH2:20][C@H:19]([CH3:21])[N:18]2[C:5](=[C:6]([O:22][CH3:23])[C:7]3[C:12](=[O:13])[NH:11][N:10]=[C:9]([C:14]([NH:16][CH3:17])=[O:15])[C:8]=32)[C:4]1=[O:24])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Cl:35][C:36]1[CH:37]=[C:38]([CH:41]=[CH:42][C:43]=1[F:44])[CH2:39]Br>CN(C=O)C>[Cl:35][C:36]1[CH:37]=[C:38]([CH:41]=[CH:42][C:43]=1[F:44])[CH2:39][N:11]1[C:12](=[O:13])[C:7]2[C:6]([O:22][CH3:23])=[C:5]3[C:4](=[O:24])[N:3]([CH2:1][CH3:2])[CH2:20][C@H:19]([CH3:21])[N:18]3[C:8]=2[C:9]([C:14]([NH:16][CH3:17])=[O:15])=[N:10]1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 27575424-(Bromomethyl)-2-chloro-1-fluorobenzeneHCID 68864941HCID 68864941, compound

Product 1

HCID 68865408HCID 68865408, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cold (0° C.) solution of (6S)-8-ethyl-10-methoxy-N,6-dimethyl-1,9-dioxo-1,2,6,7,8,9-hexahydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazine-4-carboxamide (1.58 g, 4.73 mmol) in anhydrous DMF (50 mL), a solution of lithium bis(trimethylsilyl)amide (4.97 mL, 4.97 mmol, 1 M in THF) was added. After stirring at the same temperature for 25 minutes, 3-chloro-4-fluorobenzyl bromide (1.27 g, 5.68 mmol) was added. The reaction mixture was stirred at room temperature for 10 minutes and concentrated under vacuum. The residue was partitioned between chloroform and brine. The organic extract was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with a 1-5% methanol in ethyl acetate gradient. Collection and concentration of appropriate fractions provided the title compound.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 10 minutes
  2. concentrationconcentrated under vacuum
  3. customThe residue was partitioned between chloroform and brine
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum
  8. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-16616f68f67e49638b21668a80e52b39
Source dataset
uspto-grants-2009_05
Patent number
US07538112B2

Reaction notes

Loading…