Methyl iodide → (S)-6-{3-(N-tert-butoxycarbonyl-N-methylamino)pyrrolidin-1-ylsulfonyl}isoquinoline

HRID 1845954Notes

Reaction equation

HRID 1845954 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([NH:10][C@H:11]1[CH2:15][CH2:14][N:13]([S:16]([C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[CH:25]=[N:24][CH:23]=[CH:22]3)(=[O:18])=[O:17])[CH2:12]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:29]I>CN(C)C=O>[C:3]([O:7][C:8]([N:10]([C@H:11]1[CH2:15][CH2:14][N:13]([S:16]([C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[CH:25]=[N:24][CH:23]=[CH:22]3)(=[O:18])=[O:17])[CH2:12]1)[CH3:29])=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66727094(S)-6-{3-(tert-butoxycarbonylamino)pyrrolidin-1-ylsulfonyl}isoquinoline

Product 1

HCID 66726878(S)-6-{3-(N-tert-butoxycarbonyl-N-methylamino)pyrrolidin-1-ylsulfonyl}isoquinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

265 mg of sodium hydride was added with stirring under ice cooling to an N,N-dimethylformamide (10 mL) solution of 500 mg of (S)-6-{3-(tert-butoxycarbonylamino)pyrrolidin-1-ylsulfonyl}isoquinoline obtained in Step 1. After stirring in this state for 30 minutes, 0.8 mL of methyl iodide was added dropwise to the reaction solution, and the mixture was further stirred for 30 minutes for reaction. The reaction was terminated by the dropwise addition of water in small portions under ice cooling to the reaction solution. Then, 50 mL of water was added thereto, followed by three extractions with 50 mL of ether. The combined organic layer was washed with 100 mL of saturated saline and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated, and the obtained crude product was purified by silica gel column chromatography (acetone:hexane=1:1) to obtain 100 mg of the compound of interest as a colorless oil (19%).

Workup

  1. stirringthe mixture was further stirred for 30 minutes for reaction
  2. customThe reaction was terminated by the dropwise addition of water in small portions under ice cooling to the reaction solution
  3. additionThen, 50 mL of water was added
  4. extractionfollowed by three extractions with 50 mL of ether
  5. washThe combined organic layer was washed with 100 mL of saturated saline
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationAfter filtration
  8. concentrationthe filtrate was concentrated
  9. customthe obtained crude product
  10. customwas purified by silica gel column chromatography (acetone:hexane=1:1)

Sources & evidence

ORD record
ord-dd07e0266acf4c63b376d2c48109ad61
Source dataset
uspto-grants-2015_02
Patent number
US08951997B2

Reaction notes

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