Dichloromethane → HCID 57941476, compound

HRID 1438027Notes

Reaction equation

HRID 1438027 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[N:26]=[C:27]([CH3:30])[S:28][CH:29]=1.ClCCl>[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[N:26]=[C:27]([CH3:30])[S:28][CH:29]=1

Participants

6

Reactant 3

HCID 6344DichloromethaneHCID 7363414-(Chloromethyl)-2-methyl-1,3-thiazoleHCID 57941339(4s,7r)-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 57941476HCID 57941476, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 14; 100 mg, 0.33 mmol), tetrabutylammonium iodide (120 mg, 0.32 mmol) and 4-(chloromethyl)-2-methylthiazole (Maybridge plc, Tintagel, Cornwall, UK; 197 mg, 1.3 mmol) in dimethylformamide (2 mL) was heated at 100° C. overnight. Dichloromethane (50 mL) was added and the solution was washed with 1:1 water/brine (2×25 mL) and the combined aqueous washes were back-extracted with dichloromethane (50 mL). The combined organic extracts were washed with saturated aqueous sodium thiosulfate (50 mL), and brine (50 mL). The solution was dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 50-70% ethyl acetate/petroleum ether, to give (4S,7R)-2-(2,4-difluoro-phenyl)-7,8,8-trimethyl-1-(2-methyl-thiazol-4-ylmethyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (59 mg, 43%) as a light tan solid. APCI(+)-MS (M+H) 416.

Workup

  1. washthe solution was washed with 1:1 water/brine (2×25 mL)
  2. extractionthe combined aqueous washes were back-extracted with dichloromethane (50 mL)
  3. washThe combined organic extracts were washed with saturated aqueous sodium thiosulfate (50 mL), and brine (50 mL)
  4. dry with materialThe solution was dried (magnesium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by column chromatography
  8. washeluting with 50-70% ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-a34a05fc5c5a4ef09882245f8ef68e48
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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