2,6-Lutidine → 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

HRID 2201245Notes

Reaction equation

HRID 2201245 reaction equation
FC(F)(F)S([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])(=O)=O.[F:16][C:17]1[CH:18]=[C:19]([C:23]2[N:24]([CH2:36][CH:37]([CH2:42]O)[CH2:38][C:39]([O-:41])=[O:40])[CH:25]=[C:26]3[C:31]=2[C:30](=[O:32])[N:29]([CH3:33])[C:28](=[O:34])[N:27]3[CH3:35])[CH:20]=[CH:21][CH:22]=1.[Na+].N1C(C)=CC=CC=1C.Cl.N1C=CC=CC=1>C(Cl)Cl.O>[Si:7]([O:6][CH2:42][CH:37]([CH2:36][N:24]1[C:23]([C:19]2[CH:20]=[CH:21][CH:22]=[C:17]([F:16])[CH:18]=2)=[C:31]2[C:26]([N:27]([CH3:35])[C:28](=[O:34])[N:29]([CH3:33])[C:30]2=[O:32])=[CH:25]1)[CH2:38][C:39]([OH:41])=[O:40])([C:10]([CH3:11])([CH3:12])[CH3:13])([CH3:8])[CH3:9]

Participants

7

Reactant 4

HCID 79372,6-Lutidine2×HCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonate2×HCID 10176127Pyridinium chlorideHCID 86723479Sodium 4-(5-(3-fluorophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)-3-(hydroxymethyl)butanoate

Product 1

HCID 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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

A solution of tert-butyldimethylsilyl trifluoromethanesulfonate (3.37 mL, 14.7 mmol) in DCM (5 mL) was added dropwise to a suspension of sodium 4-(5-(3-fluorophenyl)-1,3-dimethyl-2,4-dioxo-3,4-dihydro-1H-pyrrolo[3,4-d]pyrimidin-6(2H)-yl)-3-(hydroxymethyl)butanoate (1.51 g, 3.7 mmol) and 2,6-lutidine (2.57 mL, 22.0 mmol) in DCM (20 mL) at 0° C. The mixture was stirred at room temperature for 3 hours. Further portions of 2,6-lutidine (641 μL, 5.5 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate (843 μL, 3.7 mmol) were added and the mixture stirred for a further 2 hours. The reaction was diluted with DCM (50 mL), washed with water (2×25 mL) and 1M HCl(aq) (1×25 mL), the organic phase was dried over magnesium sulfate and evaporated under vacuum. The residue was suspended in methanol (25 mL) and pyridine hydrochloride (424 mg, 3.7 mmol) and water (2.5 mL) were added. The mixture was stirred at room temperature for 2 hours then concentrated under vacuum. The residue was dissolved in DCM (50 mL) and washed with 1M HCl (aq) (2×25 mL) and brine (1×25 mL). The organic phase was dried over magnesium sulfate and evaporated under vacuum. Trituration with diethyl ether afforded the title compound.

Workup

  1. stirringthe mixture stirred for a further 2 hours
  2. washwashed with water (2×25 mL) and 1M HCl(aq) (1×25 mL)
  3. dry with materialthe organic phase was dried over magnesium sulfate
  4. customevaporated under vacuum
  5. stirringThe mixture was stirred at room temperature for 2 hours
  6. concentrationthen concentrated under vacuum
  7. dissolutionThe residue was dissolved in DCM (50 mL)
  8. washwashed with 1M HCl (aq) (2×25 mL) and brine (1×25 mL)
  9. dry with materialThe organic phase was dried over magnesium sulfate
  10. customevaporated under vacuum

Sources & evidence

ORD record
ord-df791974bc9a4e0a83b238437212ba28
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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