Tetrahydrofuran → HCID 68865350, compound

HRID 494138Notes

Reaction equation

HRID 494138 reaction equation
[NH2:1][C:2]1[C:7]2[N:8]3[C@@H:16]([CH3:17])[CH2:15][N:14]([CH2:18][CH3:19])[C:13](=[O:20])[C:9]3=[C:10]([O:11][CH3:12])[C:6]=2[C:5](=[O:21])[NH:4][N:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.[F:37][C:38]1[CH:45]=[CH:44][C:41]([CH2:42]Br)=[CH:40][C:39]=1[Cl:46]>CN(C=O)C>[NH2:1][C:2]1[C:7]2[N:8]3[C@@H:16]([CH3:17])[CH2:15][N:14]([CH2:18][CH3:19])[C:13](=[O:20])[C:9]3=[C:10]([O:11][CH3:12])[C:6]=2[C:5](=[O:21])[N:4]([CH2:42][C:41]2[CH:44]=[CH:45][C:38]([F:37])=[C:39]([Cl:46])[CH:40]=2)[N:3]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 2733832Lithium HexamethyldisilazideHCID 27575424-(Bromomethyl)-2-chloro-1-fluorobenzeneHCID 68864679(6S)-4-Amino-8-ethyl-10-methoxy-6-methyl-7,8-dihydropyrazino[1',2':1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione

Product 1

HCID 68865350HCID 68865350, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (6S)-4-amino-8-ethyl-10-methoxy-6-methyl-7,8-dihydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione (0.94 g, 3.23 mmol) in anhydrous DMF (32 mL) under an atmosphere of nitrogen, a solution of lithium bis(trimethylsilyl)amide in THF (3.87 mL, 1 M, 3.87 mmol) was added. The mixture was stirred at room temperature for 15 minutes and treated with 4-fluoro-3-chlorobenzyl bromide (0.72 g, 3.23 mmol). The reaction mixture was stirred at room temperature for 1 hour and concentrated under vacuum. The residue was partitioned between chloroform and dilute hydrochloric acid. The organic extract was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluting with 0-20% methanol in ethyl acetate gradient. Collection and concentration of appropriate fractions provided the title material.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 1 hour
  2. concentrationconcentrated under vacuum
  3. customThe residue was partitioned between chloroform and dilute hydrochloric acid
  4. extractionThe organic extract
  5. washwas washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customCollection and concentration of appropriate fractions

Sources & evidence

ORD record
ord-a1523c52198b410a980a850b7faf3dcb
Source dataset
uspto-grants-2009_05
Patent number
US07538112B2

Reaction notes

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