Potassium Carbonate → 8-[2-cyano-7-(2-cyclohexyl-ethyl)-7H-pyrrolo[2,3-d]pyrimidin-6-ylmethyl]-2,8-diaza-spiro[4.5]decane-2-carboxylic acid tert-butyl ester

HRID 491481Notes

Reaction equation

HRID 491481 reaction equation
Br[CH2:2][C:3]1[N:13]([CH2:14][CH2:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[C:6]2[N:7]=[C:8]([C:11]#[N:12])[N:9]=[CH:10][C:5]=2[CH:4]=1.[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][C:31]2([CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[C:22]([O:26][C:27]([N:29]1[CH2:33][CH2:32][C:31]2([CH2:38][CH2:37][N:36]([CH2:2][C:3]3[N:13]([CH2:14][CH2:15][CH:16]4[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]4)[C:6]4[N:7]=[C:8]([C:11]#[N:12])[N:9]=[CH:10][C:5]=4[CH:4]=3)[CH2:35][CH2:34]2)[CH2:30]1)=[O:28])([CH3:25])([CH3:23])[CH3:24]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 34178604tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylateHCID 689799206-Bromomethyl-7-(2-cyclohexyl-ethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile

Product 1

HCID 689806158-[2-cyano-7-(2-cyclohexyl-ethyl)-7H-pyrrolo[2,3-d]pyrimidin-6-ylmethyl]-2,8-diaza-spiro[4.5]decane-2-carboxylic acid tert-butyl esterYield 71%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-bromomethyl-7-(2-cyclohexyl-ethyl)-7H-pyrrolo[2,3-d]pyrimidine-2-carbonitrile (290 mg, 0.84 mmol) in DMF (1.7 ml), 2,8-Diaza-spiro[4.5]decane-2-carboxylic acid tert-butyl ester (201 mg, 0.84 mmol) and potassium carbonate (138 mg, 1.0 mmol) are added. The mixture is stirred at room temperature under nitrogen atomosphere for 14 h. The reaction mixture is diluted with water and extracted with AcOEt (twice). The combined organic layer is washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue is purified by silica gel column chromatography (n-hexane:AcOEt=1:1) to give 8-[2-Cyano-7-(2-cyclohexyl-ethyl)-7H-pyrrolo[2,3-d]pyrimidin-6-ylmethyl]-2,8-diaza-spiro[4.5]decane-2-carboxylic acid tert-butyl ester in 71% yield. Rf=0.45(n-hexane:AcOEt=1:1).

Workup

  1. extractionextracted with AcOEt (twice)
  2. washThe combined organic layer is washed with water and brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by silica gel column chromatography (n-hexane:AcOEt=1:1)

Sources & evidence

ORD record
ord-3f6c91a2e57b486c8f88d94666f72406
Source dataset
uspto-grants-2009_05
Patent number
US07531546B2

Reaction notes

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