4-(Chloromethyl)-2-methyl-1,3-thiazole → HCID 57941333, compound

HRID 1438084Notes

Reaction equation

HRID 1438084 reaction equation
[CH2:1]([N:8]1[C:16]2[C@:15]3([CH3:20])[C:17]([CH3:19])([CH3:18])[C@@H:12]([CH2:13][CH2:14]3)[C:11]=2[C:10](=[O:21])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:23][C:24]1[N:25]=[C:26]([CH3:29])[S:27][CH:28]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH2:1]([N:8]1[C:16]2[C@:15]3([CH3:20])[C:17]([CH3:18])([CH3:19])[C@@H:12]([CH2:13][CH2:14]3)[C:11]=2[C:10](=[O:21])[N:9]1[CH2:23][C:24]1[N:25]=[C:26]([CH3:29])[S:27][CH:28]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 7363414-(Chloromethyl)-2-methyl-1,3-thiazole2×HCID 57941345HCID 57941345, compound2×

Product 1

HCID 57941333HCID 57941333, compoundYield 61.5%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
110 °C

Procedure

A solution of (4R,7S)-1-benzyl-7,8,8-trimethyl-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (Intermediate 49; 109 mg, 0.38 mmol), tetrabutylammonium iodide (147 mg, 0.39 mmol) and 4-(chloromethyl)-2-methylthiazole (Maybridge plc, Tintagel, Cornwall, UK; 60 mg, 0.40 mmol) in dimethylformamide (3.9 mL) was heated at 100° C. for 24 h. A second portion of 4-(chloromethyl)-2-methylthiazole (120 mg, 0.81 mmol) was added and the mixture was heated at 110° C. overnight. The solvent was evaporated and dichloromethane (100 mL) was added. The solution was washed with saturated aqueous sodium thiosulfate (150 mL), saturated aqueous sodium hydrogen carbonate (150 mL) and brine (150 mL), dried (sodium sulfate), filtered, evaporated and purified using a Biotage 40S system, eluting with 2% methanol/dichloromethane, to give (4R,7S)-1-benzyl-7,8,8-trimethyl-2-(2-methyl-thiazol-4-ylmethyl)-1,2,4,5,6,7-hexahydro-4,7-methano-indazol-3-one (92 mg, 61%) as a reddish-brown semi-solid. APCI(+)-MS (M+H) 394.

Workup

  1. customThe solvent was evaporated
  2. additiondichloromethane (100 mL) was added
  3. washThe solution was washed with saturated aqueous sodium thiosulfate (150 mL), saturated aqueous sodium hydrogen carbonate (150 mL) and brine (150 mL)
  4. dry with materialdried (sodium sulfate)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified
  8. washeluting with 2% methanol/dichloromethane

Sources & evidence

ORD record
ord-79df38997fd546ae95e6e8861a91bc6f
Source dataset
uspto-grants-2009_11
Patent number
US07622492B2

Reaction notes

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