Methyl iodide → HCID 58406333, compound

HRID 1910902Notes

Reaction equation

HRID 1910902 reaction equation
[OH:1][C:2]1[N:7]=[CH:6][C:5]([C:8]23[N:20]([C:21]([C:23]4[C:24]([CH3:28])=[N:25][O:26][CH:27]=4)=[O:22])[CH2:19][CH2:18][N:9]2[C:10](=[O:17])[C:11]2[N:12]([CH:14]=[CH:15][CH:16]=2)[CH2:13]3)=[CH:4][CH:3]=1.[C:29](=O)([O-])[O-].[Cs+].[Cs+].CI>CN(C=O)C.O>[CH3:28][C:24]1[C:23]([C:21]([N:20]2[C:8]3([C:5]4[CH:4]=[CH:3][C:2](=[O:1])[N:7]([CH3:29])[CH:6]=4)[CH2:13][N:12]4[CH:14]=[CH:15][CH:16]=[C:11]4[C:10](=[O:17])[N:9]3[CH2:18][CH2:19]2)=[O:22])=[CH:27][O:26][N:25]=1

Participants

6

Reactant 3

HCID 6328Methyl iodide2×HCID 10796Cesium carbonate2×HCID 178434715HCID 178434715, compound

Product 1

HCID 58406333HCID 58406333, compoundYield 164%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 10a-(6-hydroxypyridin-3-yl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (142) (20 mg, 0.053 mmol) and cesium carbonate (10 mg, 0.031 mmol) in DMF (2 mL) was added methyl iodide (20 μL, 0.32 mmol). LCMS after 2.5 hours showed approx. 50% conversion so extra methyl iodide (30 μL, 0.48 mmol) was added. LCMS after a further 1.75 hours showed no additional progress, so extra cesium carbonate (15 mg, 0.046 mmol) was added. LCMS after 1.5 hours showed the reaction was almost complete, and after 2 hours the mixture was diluted with water (approx. 10 mL) and freeze-dried to yield a white solid. The solid was partitioned between water (5 mL) and dichloromethane (5 mL). The organic layer was separated and the aqueous layer extracted with dichloromethane (2×5 mL). The organic layers were combined, dried (MgSO4), and concentrated in vacuo to yield a white solid. The material was purified by flash chromatography using the Biotage SP4 (4 g cartridge, dichloromethane 3 CV, 0 to 10% methanol-dichloromethane 20 CV, hold 5 CV) and freeze-dried from acetonitrile-water to give 1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-10a-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (143) as a white solid (20 mg, 96%).

Workup

  1. waitLCMS after a further 1.75 hours showed
  2. waitLCMS after 1.5 hours showed
  3. customfreeze-dried
  4. customto yield a white solid
  5. customThe solid was partitioned between water (5 mL) and dichloromethane (5 mL)
  6. customThe organic layer was separated
  7. extractionthe aqueous layer extracted with dichloromethane (2×5 mL)
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customto yield a white solid
  11. customThe material was purified by flash chromatography
  12. dry with materialfreeze-dried from acetonitrile-water

Sources & evidence

ORD record
ord-4ad0171d9cd944319e9c9600f5fc4b8f
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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