Dimethylformamide → (3-Methoxy-pyrrolidin-1-yl)-[7-chloro-thieno[3,2-b]pyridin-2-yl]-methanone

HRID 1063187Notes

Reaction equation

HRID 1063187 reaction equation
[H-].[Na+].[OH:3][CH:4]1[CH2:8][CH2:7][N:6]([C:9]([C:11]2[S:19][C:18]3[C:13](=[N:14][CH:15]=[CH:16][C:17]=3[Cl:20])[CH:12]=2)=[O:10])[CH2:5]1.[CH3:21]N(C=O)C>>[CH3:21][O:3][CH:4]1[CH2:8][CH2:7][N:6]([C:9]([C:11]2[S:19][C:18]3[C:13](=[N:14][CH:15]=[CH:16][C:17]=3[Cl:20])[CH:12]=2)=[O:10])[CH2:5]1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 22143479(7-Chloro-thieno[3,2-b]pyridin-2-yl)-(3-hydroxy-pyrrolidin-1-yl)-methanone

Product 1

HCID 22143527(3-Methoxy-pyrrolidin-1-yl)-[7-chloro-thieno[3,2-b]pyridin-2-yl]-methanoneYield 50%

Procedure

NaH (0.07 g, 1.3 mmol) was added to a solution of (+/−)-(3-hydroxy-pyrrolidin-1-yl)-[7-chloro-thieno[3,2-b]pyridin-2-yl]-methanone (0.25 g, 0.88 mmol) in DMF (10 mL), at 0° C. The reaction mixture was allowed to stir for 20 min, and Mel (0.188 g, 1.33 mmol) was added dropwise. After 3 h the reaction was quenched with saturated aqueous KCN (10 mL). The aqueous layer was extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried (Na2SO4), and the solvent was removed. Purification by flash chromatography on silica gel (CH2Cl2/MeOH 94:6) afforded the title compound as a white solid (0.13 g, 50%). MS: 297/299 (MH+); HPLC Rf: 4.11 min; HPLC purity: 93%.

Workup

  1. additionMel (0.188 g, 1.33 mmol) was added dropwise
  2. customAfter 3 h the reaction was quenched with saturated aqueous KCN (10 mL)
  3. extractionThe aqueous layer was extracted with CH2Cl2 (3×10 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. customthe solvent was removed
  6. customPurification by flash chromatography on silica gel (CH2Cl2/MeOH 94:6)

Sources & evidence

ORD record
ord-902da74580e74993840faf7ed8abf628
Source dataset
uspto-grants-2005_11
Patent number
US06964961B2

Reaction notes

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