Water → 7-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diaza-spiro[2.5]octane-4-sulfonic acid methyl-(3-phenyl-propyl)-amide

HRID 589965Notes

Reaction equation

HRID 589965 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+].Br[CH2:37][CH2:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.O>CN(C=O)C>[CH3:27][N:26]([CH2:37][CH2:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)[S:25]([N:20]1[CH2:19][CH2:18][N:17]([C:16]2[C:11]3[CH:10]=[CH:9][NH:8][C:12]=3[N:13]=[CH:14][N:15]=2)[CH2:24][C:21]21[CH2:22][CH2:23]2)(=[O:29])=[O:28]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 12503(3-Bromopropyl)benzeneHCID 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 682960107-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diaza-spiro[2.5]octane-4-sulfonic acid methyl-(3-phenyl-propyl)-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
35 °C

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) (0.71 mmol) was dissolved in dry DMF (0.5 mL) and added Cs2CO3 (0.85 mmol) and (3-bromo-propyl)-benzene (0.085 mmol). Stirred at 35° C. for 1.5 h and then added H2O (2 mL). Extracted with EtOAc (3×2 mL) and the combined organic phases were concentrated in vacuo. The residual oil was treated with TFA (2 mL) at rt→45° C. for 1.5 h. The crude reaction mixture was concentrated in vacuo and redissolved in DMSO (0.5 mL). The pure compounds were obtained by standard preparative HPLC purification of the reaction mixture.

Workup

  1. extractionExtracted with EtOAc (3×2 mL)
  2. concentrationthe combined organic phases were concentrated in vacuo
  3. additionThe residual oil was treated with TFA (2 mL) at rt→45° C. for 1.5 h
  4. customThe crude reaction mixture
  5. concentrationwas concentrated in vacuo
  6. dissolutionredissolved in DMSO (0.5 mL)
  7. customThe pure compounds were obtained by standard preparative HPLC purification of the reaction mixture

Sources & evidence

ORD record
ord-06f5e679552a426cbdcb6ab3f6925d09
Source dataset
uspto-grants-2016_01
Patent number
US09233964B2

Reaction notes

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