Imidazole → 7-(4-((tert-Butyldimethylsilyl)oxy)-1-(4-chlorothiazol-2-yl)-3-hydroxybutyl)-5-(3-fluorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

HRID 2201259Notes

Reaction equation

HRID 2201259 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl:9][C:10]1[N:11]=[C:12]([CH:15]([C:21]2[NH:22][C:23]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=3)=[C:24]3[C:29](=[O:30])[N:28]([CH3:31])[C:27](=[O:32])[N:26]([CH3:33])[C:25]=23)[CH2:16][CH:17]([OH:20])[CH2:18][OH:19])[S:13][CH:14]=1.N1C=CN=C1>CN(C1C=CN=CC=1)C.CN(C=O)C.CCOC(C)=O>[Si:1]([O:19][CH2:18][CH:17]([OH:20])[CH2:16][CH:15]([C:21]1[NH:22][C:23]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=2)=[C:24]2[C:29](=[O:30])[N:28]([CH3:31])[C:27](=[O:32])[N:26]([CH3:33])[C:25]=12)[C:12]1[S:13][CH:14]=[C:10]([Cl:9])[N:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chloride2×HCID 867234997-(1-(4-Chlorothiazol-2-yl)-3,4-dihydroxybutyl)-5-(3-fluorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Product 1

HCID 867235007-(4-((tert-Butyldimethylsilyl)oxy)-1-(4-chlorothiazol-2-yl)-3-hydroxybutyl)-5-(3-fluorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyldimethylsilyl chloride (309 mg, 2.047 mmol) was added to a solution of 7-(1-(4-chlorothiazol-2-yl)-3,4-dihydroxybutyl)-5-(3-fluorophenyl)-1,3-dimethyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione (817 mg, 1.706 mmol), imidazole (232 mg, 3.41 mmol) and DMAP (20.84 mg, 0.171 mmol) in DMF (15 mL). The mixture was stirred at room temperature for 50 mins. A further portion of tert-butyldimethylsilyl chloride (100 mg, 0.662 mmol) was added and the mixture stirred for a further 1 hour. The reaction mixture was diluted with EtOAc and washed with 0.1M HCl(aq) (1×) and brine (3×). The organic phase was dried over sodium sulfate and evaporated under vacuum. Purification by chromatography on silica, eluting with 0-60% EtOAc/hexane, afforded the title compound as a mixture of diastereomers.

Workup

  1. stirringthe mixture stirred for a further 1 hour
  2. washwashed with 0.1M HCl(aq) (1×) and brine (3×)
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. customevaporated under vacuum
  5. customPurification by chromatography on silica
  6. washeluting with 0-60% EtOAc/hexane

Sources & evidence

ORD record
ord-63b8b56b5ff340ae9568da4e7f38f557
Source dataset
uspto-grants-2016_06
Patent number
US09359381B2

Reaction notes

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