Methyl iodide → HCID 67480087, compound

HRID 1752285Notes

Reaction equation

HRID 1752285 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[NH:10][C:9](=[O:11])[N:8]([C@@H:12]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]3)[C:5]2=[N:6][CH:7]=1.[H-].[Na+].[CH3:26]I>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[N:10]([CH3:26])[C:9](=[O:11])[N:8]([C@@H:12]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]3)[C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67479945HCID 67479945, compound

Product 1

HCID 67480087HCID 67480087, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (R)-tert-butyl 3-(6-chloro-2-oxo-1H-imidazo[4,5-b]pyridin-3(2H)-yl)pyrrolidine-1-carboxylate (110 mg, 0.33 mmol) in dry THF (5 mL) was added 60% NaH in oil (20 mg, 0.5 mmol). The mixture was stirred at rt for 5 min and MeI (0.02 mL, 0.33 mmol) was added. The mixture was stirred overnight, diluted with EtOAc (100 mL), washed with brine (2×10 mL) and dried over Na2SO4. Removal of the solvent left an oil (118 mg) which was applied to a 2-g silica SPE cartridge. The cartridge was eluted sequentially with 0, 25, 50, 75 and 100% EtOAc in hexanes (15 mL of each) to afford 5 fractions. Fractions 2 & 3 were pooled and concentrated to give (R)-tert-butyl 3-(6-chloro-1-methyl-2-oxo-1H-imidazo[4,5-b]pyridin-3(2H)-yl)pyrrolidine-1-carboxylate (109 mg, 95%) as a red oil. LC-MS Method 1 tR=1.82 min, m/z=353, 279.

Workup

  1. stirringThe mixture was stirred overnight
  2. washwashed with brine (2×10 mL)
  3. dry with materialdried over Na2SO4
  4. customRemoval of the solvent
  5. waitleft an oil (118 mg) which
  6. washThe cartridge was eluted sequentially with 0, 25, 50, 75 and 100% EtOAc in hexanes (15 mL of each)
  7. customto afford 5 fractions
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-89db563907294917ab471b1b19b9c549
Source dataset
uspto-grants-2015_10
Patent number
US09163012B2

Reaction notes

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