Sodium Methoxide → (2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-1-methylpyrrolidin-2-one

HRID 74961Notes

Reaction equation

HRID 74961 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15](S(C)=O)[C:14]([F:20])=[CH:13][N:12]=3)=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:5]2=[N:6][CH:7]=1.[NH2:31][CH:32]1[CH2:36][CH2:35][N:34]([CH3:37])[C:33]1=[O:38].C[O-].[Na+]>CC(N(C)C)=O.CO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[N:16]=[C:15]([NH:31][CH:32]4[CH2:36][CH2:35][N:34]([CH3:37])[C:33]4=[O:38])[C:14]([F:20])=[CH:13][N:12]=3)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 10942334Sodium MethoxideHCID 457911333-Amino-1-methylpyrrolidin-2-oneHCID 672853215-Chloro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridine

Product 1

HCID 67285899(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-ylamino)-1-methylpyrrolidin-2-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

A solution of 5-chloro-3-(5-fluoro-4-methylsulfinyl-pyrimidin-2-yl)-1-(p-tolylsulfonyl)pyrrolo[2,3-b]pyridine, 15a, (0.060 g, 0.129 mmol) in DMA (0.5 mL) was treated with 3-amino-1-methylpyrrolidin-2-one (0.030 g, 0.258 mmol) and the reaction was heated at 140° C. for 20 minutes. The reaction mixture was cooled to room temperature and then treated with 0.5 mL of 25% NaOMe in MeOH and heated at 50° C. for 15 min. The mixture was then partitioned between aqueous saturated Na2CO3 solution and EtOAc. The aqueous layer was extracted with EtOAc twice more and the combined organic phases were concentrated in vacuo. The crude material was purified by preparative HPLC. The isolated product was filtered through basic resin to remove residual TFA and provide the desired product.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. temperatureheated at 50° C. for 15 min
  3. customThe mixture was then partitioned between aqueous saturated Na2CO3 solution and EtOAc
  4. extractionThe aqueous layer was extracted with EtOAc twice more
  5. concentrationthe combined organic phases were concentrated in vacuo
  6. customThe crude material was purified by preparative HPLC
  7. filtrationThe isolated product was filtered through basic resin
  8. customto remove residual TFA

Sources & evidence

ORD record
ord-88b435afd37641d3838411c4bb6f4c48
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Reaction notes

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