Methanol → MK-2048

HRID 494120Notes

Reaction equation

HRID 494120 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][C:32]=1[F:33])[CH2:5][N:6]1[C:11](=[O:12])[C:10]2[C:13]([O:24]C)=[C:14]3[C:19](=[O:20])[N:18]([CH2:21][CH3:22])[CH2:17][C@H:16]([CH3:23])[N:15]3[C:9]=2[C:8]([C:26]([NH:28][CH3:29])=[O:27])=[N:7]1.B(Br)(Br)Br.CO>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:30]=[CH:31][C:32]=1[F:33])[CH2:5][N:6]1[C:11](=[O:12])[C:10]2[C:13]([OH:24])=[C:14]3[C:19](=[O:20])[N:18]([CH2:21][CH3:22])[CH2:17][C@H:16]([CH3:23])[N:15]3[C:9]=2[C:8]([C:26]([NH:28][CH3:29])=[O:27])=[N:7]1

Participants

5

Reactant 3

HCID 887MethanolHCID 25134Boron tribromideHCID 68865408(6S)-2-(3-Chloro-4-fluorobenzyl)-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

Product 1

HCID 54698642MK-2048

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of (6S)-2-(3-chloro-4-fluorobenzyl)-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 (1.15 g, 2.41 mmol) in anhydrous dichloromethane (800 mL), a solution of boron tribromide in dichloromethane (3.14 mL, 3.14 mmol; 1 M) was added. After stirring at room temperature for 5 minutes, the reaction mixture was treated with anhydrous methanol, stirred for 30 minutes, and concentrated under vacuum. The procedure was repeated twice. The residue was dissolved in a mixture of methanol and acetonitrile and treated with aqueous sodium hydroxide. The mixture was subjected to purification on preparative reverse phase high pressure column chromatography. Collection and lyophilization of appropriate fractions provided the title compound as white amorphous solid.

Workup

  1. stirringstirred for 30 minutes
  2. concentrationconcentrated under vacuum
  3. dissolutionThe residue was dissolved in a mixture of methanol and acetonitrile
  4. additiontreated with aqueous sodium hydroxide
  5. customThe mixture was subjected to purification on preparative reverse phase high pressure column chromatography
  6. customCollection and lyophilization of appropriate fractions

Sources & evidence

ORD record
ord-48575fe2710044cab51f129303100465
Source dataset
uspto-grants-2009_05
Patent number
US07538112B2

Reaction notes

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