Methanamine, N-methoxy-, hydrochloride (1:1) → 4-((tert-Butyldimethylsilyl)oxy)-3-((5-(3-fluorophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)methyl)-N-methoxy-N-methylbutanamide

HRID 2201246Notes

Reaction equation

HRID 2201246 reaction equation
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[Si:19]([O:26][CH2:27][CH:28]([CH2:33][N:34]1[C:42]([C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([F:49])[CH:44]=2)=[C:41]2[C:36]([N:37]([CH3:53])[C:38](=[O:52])[N:39]([CH3:51])[C:40]2=[O:50])=[CH:35]1)[CH2:29][C:30](O)=[O:31])([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20].CCN(C(C)C)C(C)C.Cl.[CH3:64][NH:65][O:66][CH3:67]>CN(C=O)C.C(OCC)(=O)C>[Si:19]([O:26][CH2:27][CH:28]([CH2:33][N:34]1[C:42]([C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([F:49])[CH:44]=2)=[C:41]2[C:36]([N:37]([CH3:53])[C:38](=[O:52])[N:39]([CH3:51])[C:40]2=[O:50])=[CH:35]1)[CH2:29][C:30]([N:65]([O:66][CH3:67])[CH3:64])=[O:31])([C:22]([CH3:24])([CH3:25])[CH3:23])([CH3:20])[CH3:21]

Participants

7

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 867234814-((tert-Butyldimethylsilyl)oxy)-3-((5-(3-fluorophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)methyl)butanoic acid

Product 1

HCID 867234824-((tert-Butyldimethylsilyl)oxy)-3-((5-(3-fluorophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)methyl)-N-methoxy-N-methylbutanamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

T3P® (2.62 mL, 4.5 mmol) was added to a suspension of 4-((tert-butyldimethylsilyl)oxy)-3-((5-(3-fluorophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)methyl)butanoic acid (1.13 g, 2.2 mmol), DIPEA (2.16 mL, 12.3 mmol) and N,O-dimethylhydroxylamine hydrochloride (263 mg, 2.7 mmol) in DMF (8 mL) at 0° C. The mixture was stirred at room temperature for 30 minutes. The reaction was diluted with ethyl acetate (40 mL) and was washed with water (1×20 mL), 1M HCl(aq) (1×20 mL) and saturated NaHCO3(aq) (1×20 mL). The organic phase was dried over magnesium sulfate and the solvent was removed under vacuum. Purification by chromatography on silica, eluting with 0-3% MeOH/DCM, afforded the title compound.

Workup

  1. washwas washed with water (1×20 mL), 1M HCl(aq) (1×20 mL) and saturated NaHCO3(aq) (1×20 mL)
  2. dry with materialThe organic phase was dried over magnesium sulfate
  3. customthe solvent was removed under vacuum
  4. customPurification by chromatography on silica
  5. washeluting with 0-3% MeOH/DCM

Sources & evidence

ORD record
ord-d050db0a54ed4089b53d194c06710530
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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