Potassium Carbonate → HCID 17968178, compound

HRID 271587Notes

Reaction equation

HRID 271587 reaction equation
[CH2:1]([N:3]1[C:7]2([CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[C:6](=[O:13])[NH:5][C:4]1=[O:14])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:22][C:23]1[N:33]([CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])[C:26]2[N:27]=[C:28]([C:31]#[N:32])[N:29]=[CH:30][C:25]=2[CH:24]=1>CS(C)=O>[CH3:36][C:35]([CH3:38])([CH3:37])[CH2:34][N:33]1[C:26]2[N:27]=[C:28]([C:31]#[N:32])[N:29]=[CH:30][C:25]=2[CH:24]=[C:23]1[CH2:22][N:10]1[CH2:11][CH2:12][C:7]2([N:3]([CH2:1][CH3:2])[C:4](=[O:14])[NH:5][C:6]2=[O:13])[CH2:8][CH2:9]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 113128256-Bromomethyl-7-(2,2-dimethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrileHCID 17968236HCID 17968236, compound

Product 1

HCID 17968178HCID 17968178, compoundYield 49.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 2,4-dioxo-1,3,8-triaza-spiro[4.5]decane-3,8-dicarboxylic acid di-tert-butyl ester (0.4 g, 1.1 mmol) in DMF (8 ml), NaH (80 mg, 2.2 mmol) and ethyl bromide (166 □1, 2.16 mmol) are added at room temperature. The reaction mixture is stirred at ambient temperature for 15 h, quenched with saturated ammonium clroride and extracted with AcOEt. The organic layer is washed with brine, dried over magnesium sulfate and filtrated. To a solution of 1-ethyl-2,4-dioxo-1,3,8-triaza-spiro[4.5]decane-3,8-dicarboxylic acid di-tert-butyl ester (1.1 mmol) in CH2Cl2 (10 ml), TFA (10 ml) are added at 0° C. The reaction mixture is stirred at room temperature for 1 h. After removal of the solvent, ethyl ether is added to the residue to give 34 mg of desired product in 10% yield. To a solution of 1-ethyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione (30 mg, 0.096 mmol) in DMSO (1 ml), potassium carbonate (13.8 mg, 0.1 mmol) and 6-bromomethyl-7-(2,2-dimethyl-propyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile (30.7 mg, 0.1 mmol) are added to the mixture at ambient temperature. The reaction mixture is stirred at ambient temperature for 3 h, quenched with saturated ammonium clroride 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 reverse phase preparative HPLC to give 20 mg of desired product in 3.6% yield.

Workup

  1. customquenched with saturated ammonium clroride
  2. extractionextracted with AcOEt
  3. washThe combined extracts are washed with H2O, brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationThe combined extracts are concentrated
  6. customthe residue is purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-e8518a5985fe4e0b987a987348a470b2
Source dataset
uspto-grants-2008_11
Patent number
US07452886B2

Reaction notes

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