Bromide ion → 7-(2,2-Dimethyl-propyl)-6-(3-methyl-2,4-dioxo-1-propyl-1,3,8-triaza-spiro[4,5]dec-8-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile

HRID 271586Notes

Reaction equation

HRID 271586 reaction equation
C(OC(N1CCC2(NC(=O)N(C)C2=O)CC1)=O)(C)(C)C.[Br-].C(O[C:27]([N:29]1[CH2:44][CH2:43][C:32]2([N:36]([CH2:37][CH2:38][CH3:39])[C:35](=[O:40])[N:34]([CH3:41])[C:33]2=[O:42])[CH2:31][CH2:30]1)=O)(C)(C)C.C(=O)([O-])[O-].[K+].[K+].BrC[C:53]1[N:63]([CH2:64][C:65]([CH3:68])([CH3:67])[CH3:66])[C:56]2[N:57]=[C:58]([C:61]#[N:62])[N:59]=[CH:60][C:55]=2[CH:54]=1>CN(C=O)C.C(Cl)Cl.C(O)(C(F)(F)F)=O.CS(C)=O>[CH3:66][C:65]([CH3:68])([CH3:67])[CH2:64][N:63]1[C:56]2[N:57]=[C:58]([C:61]#[N:62])[N:59]=[CH:60][C:55]=2[CH:54]=[C:53]1[CH2:27][N:29]1[CH2:30][CH2:31][C:32]2([N:36]([CH2:37][CH2:38][CH3:39])[C:35](=[O:40])[N:34]([CH3:41])[C:33]2=[O:42])[CH2:43][CH2:44]1

Participants

10

Reactant 5

HCID 259Bromide ionHCID 11430Potassium CarbonateHCID 113128256-Bromomethyl-7-(2,2-dimethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrileHCID 18931276Tert-butyl 3-methyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decane-8-carboxylateHCID 598346163-Methyl-2,4-dioxo-1-propyl-1,3,8-triaza-spiro[4,5]decane-8-carboxylic acid tert-butyl ester

Product 1

HCID 179682027-(2,2-Dimethyl-propyl)-6-(3-methyl-2,4-dioxo-1-propyl-1,3,8-triaza-spiro[4,5]dec-8-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrileYield 37.5%

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 3-methyl-2,4-dioxo-1,3,8-triaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (1 g, 3.53 mmol) in DMF (10 ml), Na (211 mg, 5.4 mmol) and n-propryl bromide (384 □1, 4.24 mmol) are added at 0° C. The reaction mixture is stirred at ambient temperature for 4 h, quenched with saturated ammonium chloride and extracted with AcOEt. The organic layer is washed with brine, dried over magnesium sulfate and filtrated. To a solution of 3-methyl-2,4-dioxo-1-propyl-1,3,8-triaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (3.53 mmol) in CH2Cl2 (5 ml), TFA (5 ml) are added at 0° C. The reaction mixture is stirred at room temperature for 1 h. After removal of the solvent, H2O is added to the residue and lyophilized. To the crude product (1.5 g, 4.42 mmol) in DMSO (10 ml), potassium carbonate (1.2 g, 8.82 mmol) and 6-bromomethyl-7-(2,2-dimethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile (0.7 g, 2.28 mmol) are added to the mixture at ambient temperature. The reaction mixture is stirred at ambient temperature for 3 h, quenched with saturated ammonium chloride and extracted with AcOEt. The combined extracts are washed with H2O, brine and dried over magnesium sulfate. The combined extracts are concentrated and the residue is purified by column chromatography on silica gel using n-hexane:AcOEt=3:1 to give 386 mg of desired product in 24% yield.

Workup

  1. customquenched with saturated ammonium chloride
  2. extractionextracted with AcOEt
  3. washThe organic layer is washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltrated
  6. stirringThe reaction mixture is stirred at room temperature for 1 h
  7. customAfter removal of the solvent, H2O
  8. additionis added to the residue
  9. stirringThe reaction mixture is stirred at ambient temperature for 3 h
  10. customquenched with saturated ammonium chloride
  11. extractionextracted with AcOEt
  12. washThe combined extracts are washed with H2O, brine
  13. dry with materialdried over magnesium sulfate
  14. concentrationThe combined extracts are concentrated
  15. customthe residue is purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-8bb15a2edfde49efb438114090437e77
Source dataset
uspto-grants-2008_11
Patent number
US07452886B2

Reaction notes

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