Sodium hydride → 7-(((tert-Butyldimethylsilyl)oxy)methyl)-9-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione

HRID 2201261Notes

Reaction equation

HRID 2201261 reaction equation
[H-].[Na+].CS(O[CH:8]([CH2:18][CH:19]([C:40]1[S:41][CH:42]=[C:43]([Cl:45])[N:44]=1)[C:20]1[NH:21][C:22]([C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=2)=[C:23]2[C:28](=[O:29])[N:27]([CH3:30])[C:26](=[O:31])[N:25]([CH3:32])[C:24]=12)[CH2:9][O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])(=O)=O>C1COCC1>[Si:11]([O:10][CH2:9][CH:8]1[CH2:18][CH:19]([C:40]2[S:41][CH:42]=[C:43]([Cl:45])[N:44]=2)[C:20]2[N:21]1[C:22]([C:33]1[CH:38]=[CH:37][CH:36]=[C:35]([F:39])[CH:34]=1)=[C:23]1[C:28](=[O:29])[N:27]([CH3:30])[C:26](=[O:31])[N:25]([CH3:32])[C:24]1=2)([C:14]([CH3:15])([CH3:16])[CH3:17])([CH3:12])[CH3:13]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 867235011-((tert-Butyldimethylsilyl)oxy)-4-(4-chlorothiazol-2-yl)-4-(5-(3-fluorophenyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-7-yl)butan-2-yl methanesulfonate

Product 1

HCID 867235027-(((tert-Butyldimethylsilyl)oxy)methyl)-9-(4-chlorothiazol-2-yl)-5-(3-fluorophenyl)-1,3-dimethyl-8,9-dihydro-1H-pyrimido[4,5-a]pyrrolizine-2,4(3H,7H)-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (127 mg, 3.18 mmol) was added to a solution of 1-((tert-butyldimethylsilyl)oxy)-4-(4-chlorothiazol-2-yl)-4-(5-(3-fluorophenyl)-1,3-dimethyl-2,4-dioxo-2,3,4,6-tetrahydro-1H-pyrrolo[3,4-d]pyrimidin-7-yl)butan-2-yl methanesulfonate (712 mg, 1.061 mmol) in THF (30 mL). The mixture was stirred at room temperature for 35 mins. The reaction was quenched with water and extracted with DCM (3×). The combined organic extracts were passed through a hydrophobic frit and evaporated under vacuum. Purification by chromatography on silica, eluting with 0-100% EtOAc/hexane afforded the title compound as a mixture of diastereomers.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with DCM (3×)
  3. customevaporated under vacuum
  4. customPurification by chromatography on silica
  5. washeluting with 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-a3b87136973f4e729f6a6436a5c0c5f8
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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