3-(Chloromethyl)-2-methoxypyridine → HCID 57941441, compound

HRID 1438029Notes

Reaction equation

HRID 1438029 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:21])([CH3:20])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[NH:10]1.Cl[CH2:24][C:25]1[C:26]([O:31][CH3:32])=[N:27][CH:28]=[CH:29][CH:30]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:17](=[O:18])[C:16]2[C@H:15]3[C:19]([CH3:21])([CH3:20])[C@:12]([CH3:22])([CH2:13][CH2:14]3)[C:11]=2[N:10]1[CH2:24][C:25]1[C:26]([O:31][CH3:32])=[N:27][CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 2

HCID 149329453-(Chloromethyl)-2-methoxypyridine2×HCID 57941350(4r,7s)-2-(2,4-Difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one2×

Product 1

HCID 57941441HCID 57941441, compoundYield 30.3%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4R,7S)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 42; 476 mg, 1.56 mmol), 3-chloromethyl-2-methoxy-pyridine (Intermediate 51; 989 mg, 6.3 mmol) and tetrabutylammonium iodide (580 mg, 1.6 mmol) in dimethylformamide (16 mL) was heated at 100° C. for 48 h. The solvent was evaporated and dichloromethane (250 mL) was added. The solution was washed with concentrated aqueous sodium thiosulfate (2×100 mL), saturated aqueous sodium hydrogen carbonate (100 mL), water (6×500 mL) and brine (100 mL), dried (magnesium sulfate), filtered, evaporated and purified using a Biotage 40L system, eluting with 1-2% methanol/dichcloromethane to give an oily material. This material was dried on a vacuum pump, co-evaporated three times with ethanol, and finally held again under high vacuum to give (4R,7S)-2-(2,4-difluoro-phenyl)-1-(2-methoxy-pyridin-3-ylmethyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (201 mg, 30%) as an off-white solid. ES(+)-MS (M+H) 426.

Workup

  1. customThe solvent was evaporated
  2. additiondichloromethane (250 mL) was added
  3. washThe solution was washed with concentrated aqueous sodium thiosulfate (2×100 mL), saturated aqueous sodium hydrogen carbonate (100 mL), water (6×500 mL) and brine (100 mL)
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified
  8. washeluting with 1-2% methanol/dichcloromethane
  9. customto give an oily material
  10. customThis material was dried on a vacuum pump

Sources & evidence

ORD record
ord-b572cbe1e8d0487ebb69b8949ea669ae
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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