Hydrochloric Acid → HCID 67435171, compound

HRID 408826Notes

Reaction equation

HRID 408826 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([CH2:28][CH2:29][OH:30])[C:10]2[C:15]([N:16]=1)=[C:14]([N:17]1[CH2:22][CH2:21][N:20]3[C:23](=[O:26])[CH2:24][CH2:25][CH:19]3[CH2:18]1)[N:13]=[C:12]([CH3:27])[N:11]=2.[CH3:31]I.[H-].[Na+].Cl>C(OCC)(=O)C.O.CN(C=O)C>[ClH:1].[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([CH2:28][CH2:29][O:30][CH3:31])[C:10]2[C:15]([N:16]=1)=[C:14]([N:17]1[CH2:22][CH2:21][N:20]3[C:23](=[O:26])[CH2:24][CH2:25][CH:19]3[CH2:18]1)[N:13]=[C:12]([CH3:27])[N:11]=2

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58459065HCID 58459065, compound

Product 1

HCID 67435171HCID 67435171, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Charge a 100 mL flask with 2-[8-(2-chlorophenyl)-9-(2-hydroxyethyl)-2-methyl-purin-6-yl]-1,3,4,7,8,8a-hexahydropyrrolo[1,2-a]pyrazin-6-one, Isomer-2 [C09111070-E] (3.3 g, 7.73 mmol) and DMF (35 mL) followed by methyl iodide (1.24 g, 8.50 mmol). Add 60% NaH (0.59 g, 13.9 mmol) in portions at 10-25° C. and stir for 2 h. Pour the mixture into water (100 mL) while stirring and extract the solution with ethyl acetate (3×50 mL). Combine the organic layers, wash with water (2×50 mL), and concentrate under vacuum to give an oil. Purify the crude by silica gel (100 g) column chromatography eluting with dichloromethane/methanol (50:1) to give a yellow solid. Redissolve the solid in ethyl acetate (40 mL) and add a solution of 1 N HCl in ethyl acetate slowly until a solid precipitates. Stir at room temperature for 2 h, filter the cake, and wash with ethyl acetate (10 mL). Dry the cake under vacuum to give 2.8 g of the title compound as an off-white solid (98.0% ee); ES/MS m/z 441.3 (M+1).

Workup

  1. stirringwhile stirring
  2. extractionextract the solution with ethyl acetate (3×50 mL)
  3. washCombine the organic layers, wash with water (2×50 mL)
  4. concentrationconcentrate under vacuum
  5. customto give an oil
  6. customPurify the crude by silica gel (100 g) column chromatography
  7. washeluting with dichloromethane/methanol (50:1)
  8. customto give a yellow solid
  9. customprecipitates
  10. stirringStir at room temperature for 2 h
  11. filtrationfilter the cake
  12. washwash with ethyl acetate (10 mL)
  13. customDry the cake under vacuum

Sources & evidence

ORD record
ord-08d361491a694eecbf03f5385f2cc13a
Source dataset
uspto-grants-2014_06
Patent number
US08759360B2

Reaction notes

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