Sodium Carbonate → 7-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diaza-spiro[2.5]octane-4-sulfonic acid (4-cyano-benzyl)-methyl-amide

HRID 589967Notes

Reaction equation

HRID 589967 reaction equation
C(OC([N:8]1[C:12]2[N:13]=[CH:14][N:15]=[C:16]([N:17]3[CH2:24][C:21]4([CH2:23][CH2:22]4)[N:20]([S:25](=[O:29])(=[O:28])[NH:26][CH3:27])[CH2:19][CH2:18]3)[C:11]=2[CH:10]=[CH:9]1)=O)(C)(C)C.C([O-])([O-])=O.[Cs+].[Cs+].BrC[C:38]1[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=1.[C:46]([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C(Cl)Cl.O>[C:42]([C:41]1[CH:44]=[CH:45][C:38]([CH2:27][N:26]([CH3:46])[S:25]([N:20]2[CH2:19][CH2:18][N:17]([C:16]3[C:11]4[CH:10]=[CH:9][NH:8][C:12]=4[N:13]=[CH:14][N:15]=3)[CH2:24][C:21]32[CH2:23][CH2:22]3)(=[O:28])=[O:29])=[CH:39][CH:40]=1)#[N:43]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 10796Cesium carbonateHCID 869964-(Bromomethyl)benzonitrileHCID 682959194-(4-Methylsulfamoyl-4,7-diaza-spiro[2.5]oct-7-yl)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid tert-butyl ester2×

Product 1

HCID 867064317-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diaza-spiro[2.5]octane-4-sulfonic acid (4-cyano-benzyl)-methyl-amide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

4-(4-Methylsulfamoyl-4,7-diaza-spiro[2.5]oct-7-yl)-pyrrolo[2,3-d]pyrimidine-7-carboxylic acid tert-butyl ester (intermediate 4) (0.237 mmol) was dissolved in dry DMF (2 mL) and added Cs2CO3 (0.35 mmol) and 4-bromomethyl-benzonitrile (0.35 mmol). Stirred at rt for 16 h and then added H2O (10 mL). Extracted with EtOAc (3×10 mL) and the combined organic phases were concentrated in vacuo. Purified by flash chromatography on silica using a gradient of heptane to EtOAc as eluent. The obtained compound was treated with TFA (2 mL) at rt for 2 h. The crude reaction mixture was added sat. Na2CO3 to pH=7 and the extracted with EtOAc (3×10 mL). the combined organic phases was washes with brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. The pure compound was obtained by trituation using CH2Cl2.

Workup

  1. extractionExtracted with EtOAc (3×10 mL)
  2. concentrationthe combined organic phases were concentrated in vacuo
  3. customPurified by flash chromatography on silica using a gradient of heptane to EtOAc as eluent
  4. additionThe obtained compound was treated with TFA (2 mL) at rt for 2 h
  5. customThe crude reaction mixture
  6. extractionthe extracted with EtOAc (3×10 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe pure compound was obtained by trituation

Sources & evidence

ORD record
ord-28db3ea54c484346882767c6827976cf
Source dataset
uspto-grants-2016_01
Patent number
US09233964B2

Reaction notes

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