Methanamine, N-methoxy-, hydrochloride (1:1) → 3-(1,3-Dimethyl-2,4-dioxo-5-phenyl-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)-N-methoxy-N-methylpropanamide

HRID 2201218Notes

Reaction equation

HRID 2201218 reaction equation
C([Mg]Br)(C)C.[CH3:6][N:7]1[C:12]2=[CH:13][N:14]([CH2:22][CH2:23][C:24](OC)=[O:25])[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[C:11]2[C:10](=[O:28])[N:9]([CH3:29])[C:8]1=[O:30].Cl.[CH3:32][NH:33][O:34][CH3:35]>C1COCC1>[CH3:6][N:7]1[C:12]2=[CH:13][N:14]([CH2:22][CH2:23][C:24]([N:33]([O:34][CH3:35])[CH3:32])=[O:25])[C:15]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[C:11]2[C:10](=[O:28])[N:9]([CH3:29])[C:8]1=[O:30]

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 86723437Methyl 3-(1,3-dimethyl-2,4-dioxo-5-phenyl-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)propanoateHCID 178418365HCID 178418365, compound2×

Product 1

HCID 867234563-(1,3-Dimethyl-2,4-dioxo-5-phenyl-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)-N-methoxy-N-methylpropanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Isopropylmagnesium bromide solution (2.9M, 3.03 mL, 8.79 mmol) was added slowly to a suspension of methyl 3-(1,3-dimethyl-2,4-dioxo-5-phenyl-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)propanoate (Example 11.0 step 1) (1.5 g, 4.39 mmol) and commercially available N,O-dimethylhydroxylamine hydrochloride (0.514 g, 5.27 mmol) in THF (50 mL) at 0° C. The mixture was warmed to room temperature and stirred for 30 mins. A further portion of isopropylmagnesium bromide solution (2.9M, 3.03 mL, 8.79 mmol) was added slowly and the mixture stirred for a further 60 mins. The reaction was quenched with saturated NH4Cl(aq) and extracted with EtOAc (2×). The combined organic extracts were washed with brine, dried over sodium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 50-100% EtOAc/hexane, then 1-8% MeOH/EtOAc afforded the title compound.

Workup

  1. stirringthe mixture stirred for a further 60 mins
  2. customThe reaction was quenched with saturated NH4Cl(aq)
  3. extractionextracted with EtOAc (2×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. customevaporated under vacuum
  7. customPurification by chromatography on silica
  8. washeluting with 50-100% EtOAc/hexane

Sources & evidence

ORD record
ord-9ee13f1bfc624b9caedf9b0704ea222a
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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