Methyl iodide → HCID 89924204, compound

HRID 1505693Notes

Reaction equation

HRID 1505693 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH:7]2[CH2:17][CH2:16][C:10]3([CH2:14][NH:13][C:12](=[O:15])[CH2:11]3)[CH2:9][CH2:8]2)[CH:6]=1.[H-].[Na+].[CH3:20]I>CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH:7]2[CH2:17][CH2:16][C:10]3([CH2:14][N:13]([CH3:20])[C:12](=[O:15])[CH2:11]3)[CH2:9][CH2:8]2)[CH:6]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 89935781HCID 89935781, compound2×

Product 1

HCID 89924204HCID 89924204, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 8-(4-bromo-1H-pyrazol-1-yl)-2-azaspiro[4.5]decan-3-one (mixture of intermediate 30 and 31 obtained in step 5; 4 g, 13.4 mmol) in DMF (10 mL) was added sodium hydride (60%) (0.8 g, 0.0116 mol) followed by methyl iodide (2.2 mL, 14.8 mmol) at 0° C. The reaction mixture was slowly allowed to warm to RT and stirred for 1 h. The reaction mixture was quenched with water and extracted with ethyl acetate. Combined organic phases were washed with water (50 mL) and brine (50 mL), dried over sodium sulphate, filtered and concentrated. Purification by flash chromatography on silica (Pet. ether: ethyl acetate) afforded the title compound (mixture of two isomers) as an off white solid (1.8 g, 43%). 1H NMR (400 MHz, DMSO-d6) δ 8.04-8.03 (m, 1H), 7.51-7.50 (m, 1H), 4.16-4.10 (m, 1H), 3.24 (s, 1H), 3.09 (s, 1H), 2.70-2.69 (m, 3H), 2.21 (s, 1H), 2.09 (s, 1H), 1.90-1.86 (m, 6H), 1.79-1.54 (m, 2H).

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with ethyl acetate
  3. washCombined organic phases were washed with water (50 mL) and brine (50 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash chromatography on silica (Pet. ether: ethyl acetate)

Sources & evidence

ORD record
ord-c89e428099ac4adfbda6639f14f21284
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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