Water → {Methyl-[7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diaza-spiro[2.5]octane-4-sulfonyl]-amino}-acetic acid methyl ester

HRID 589966Notes

Reaction equation

HRID 589966 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+].[CH3:36][O:37][C:38](=[O:41])[CH2:39]Cl.O>CN(C=O)C>[CH3:36][O:37][C:38](=[O:41])[CH2:39][N:26]([CH3:27])[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:28])=[O:29]

Participants

6

Reactant 4

HCID 962WaterHCID 7295Methyl chloroacetateHCID 10796Cesium carbonateHCID 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 57410569{Methyl-[7-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,7-diaza-spiro[2.5]octane-4-sulfonyl]-amino}-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °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) (0.047 mmol) was dissolved in dry DMF (0.5 mL) and added Cs2CO3 (0.071 mmol) and chloro-acetic acid methyl ester (0.071 mmol). Stirred at 40° C. for 2 h and then added H2O (1.5 mL). Extracted with EtOAc (3×1 mL) and the combined organic phases were washed with brine (1 mL) and concentrated in vacuo. The residual oil was treated with TFA (1 mL) at rt for 1 h. The crude reaction mixture was concentrated in vacuo and redissolved in DMSO (0.5 mL). The pure compound was obtained by standard preparative HPLC purification of the reaction mixture.

Workup

  1. extractionExtracted with EtOAc (3×1 mL)
  2. washthe combined organic phases were washed with brine (1 mL)
  3. concentrationconcentrated in vacuo
  4. additionThe residual oil was treated with TFA (1 mL) at rt for 1 h
  5. customThe crude reaction mixture
  6. concentrationwas concentrated in vacuo
  7. dissolutionredissolved in DMSO (0.5 mL)
  8. customThe pure compound was obtained by standard preparative HPLC purification of the reaction mixture

Sources & evidence

ORD record
ord-0f4a5bbf95aa4293b71f4ae633e5df0d
Source dataset
uspto-grants-2016_01
Patent number
US09233964B2

Reaction notes

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