Cesium carbonate → 6-(2-((tert-Butyldimethylsilyl)oxy)-3-(1,3-dioxoisoindolin-2-yl)propyl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

HRID 624580Notes

Reaction equation

HRID 624580 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:7][N:8]1[C:13]2=[CH:14][NH:15][C:16]([C:17]3[S:18][CH:19]=[C:20]([CH3:22])[N:21]=3)=[C:12]2[C:11](=[O:23])[N:10]([CH3:24])[C:9]1=[O:25].Br[CH2:27][CH:28]([O:41][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])[CH2:29][N:30]1[C:38](=[O:39])[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]1=[O:40]>CN(C)C(=O)C.O>[Si:42]([O:41][CH:28]([CH2:29][N:30]1[C:38](=[O:39])[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[C:31]1=[O:40])[CH2:27][N:15]1[C:16]([C:17]2[S:18][CH:19]=[C:20]([CH3:22])[N:21]=2)=[C:12]2[C:13]([N:8]([CH3:7])[C:9](=[O:25])[N:10]([CH3:24])[C:11]2=[O:23])=[CH:14]1)([C:45]([CH3:48])([CH3:46])[CH3:47])([CH3:44])[CH3:43]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 867229042-(3-Bromo-2-((tert-butyldimethylsilyl)oxy)propyl)isoindoline-1,3-dioneHCID 1363483951,3-dimethyl-5-(4-methylthiazol-2-yl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Product 1

HCID 867229056-(2-((tert-Butyldimethylsilyl)oxy)-3-(1,3-dioxoisoindolin-2-yl)propyl)-1,3-dimethyl-5-(4-methylthiazol-2-yl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
50 °C

Procedure

Cesium carbonate (115 mg, 0.351 mmol) was added to a solution of 1,3-dimethyl-5-(4-methylthiazol-2-yl)-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (Intermediate Gc) (53.4 mg, 0.176 mmol) and 2-(3-bromo-2-((tert-butyldimethylsilyl)oxy)propyl)isoindoline-1,3-dione (70 mg, 0.176 mmol) in N,N-dimethylacetamide (1273 μl). The mixture was heated at 50° C. for 18 hours, then cooled to room temperature and diluted with water (30 ml). The mixture was extracted with ethyl acetate (3×30 ml), the combined organic extracts were washed with brine (90 ml), dried over sodium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 0-100% EtOAc/hexane, afforded the title compound.

Workup

  1. temperaturecooled to room temperature
  2. extractionThe mixture was extracted with ethyl acetate (3×30 ml)
  3. washthe combined organic extracts were washed with brine (90 ml)
  4. dry with materialdried over sodium sulfate
  5. customevaporated under vacuum
  6. customPurification by chromatography on silica
  7. washeluting with 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-cb9ed50959d84710b216ed97f36e70b8
Source dataset
uspto-grants-2016_04
Patent number
US09303035B2

Reaction notes

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