Methyl iodide → 7-chloro-2-[(R)-3-methoxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridine

HRID 889880Notes

Reaction equation

HRID 889880 reaction equation
[H-].[Na+].[OH:3][C@@H: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]I.[C-]#N.[K+]>C1COCC1>[Cl:20][C:17]1[CH:16]=[CH:15][N:14]=[C:13]2[CH:12]=[C:11]([C:9]([N:6]3[CH2:7][CH2:8][C@@H:4]([O:3][CH3:21])[CH2:5]3)=[O:10])[S:19][C:18]=12

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 9032Potassium CyanideHCID 24758Sodium hydrideHCID 207677587-chloro-2-[(R)-3-hydroxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridine

Product 1

HCID 207677657-chloro-2-[(R)-3-methoxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridineYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (2.1 g, 53.1 mmol) was added to a solution of (3R)-(3-hydroxy-pyrrolidin-1-yl)-[7-chloro-thieno[3,2-b]pyridin-2-yl]-methanone (5.0 g, 17.7 mmol) in THF (100 mL), at 0° C. The reaction mixture was allowed to stir for 20 min., and MeI (3.26 g, 22.9 mmol) was added dropwise. After 3 h the reaction was treated with saturated aqueous KCN. The aqueous layer was extracted with CH2Cl2. The combined organic layers were dried (Na2SO4), and the solvent was removed under reduced pressure. Purification by flash chromatography on silica gel, eluting with CH2Cl2/MeOH (94:6) afforded the title compound as a white solid (3.2 g, 61%). MS: 297.2/299.2 (MH+); HPLC Rf: 4.25 min.; HPLC purity: 95%.

Workup

  1. extractionThe aqueous layer was extracted with CH2Cl2
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. customthe solvent was removed under reduced pressure
  4. customPurification by flash chromatography on silica gel
  5. washeluting with CH2Cl2/MeOH (94:6)

Sources & evidence

ORD record
ord-7eda8dbd196d4f8ba844098a932e8e18
Source dataset
uspto-grants-2006_02
Patent number
US06995171B2

Reaction notes

Loading…