Carbon Tetrachloride → HCID 69795730, compound

HRID 1071558Notes

Reaction equation

HRID 1071558 reaction equation
CC(C)(C)C([NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[N:7]=1)=[O:4].C(Cl)(Cl)(Cl)Cl.BrN1C(=O)CCC1=O.[SH:28][C:29]1[NH:30][C:31]2[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=2[N:33]=1>C(O)(C)C>[OH2:4].[NH:30]1[C:31]2[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=2[N:33]=[C:29]1[S:28][CH2:12][C:8]1[N:7]=[C:6]([NH2:5])[CH:11]=[CH:10][CH:9]=1.[NH:30]1[C:31]2[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=2[N:33]=[C:29]1[S:28][CH2:12][C:8]1[N:7]=[C:6]([NH2:5])[CH:11]=[CH:10][CH:9]=1

Participants

6

Reactant 4

HCID 5943Carbon TetrachlorideHCID 67184N-bromobutanimideHCID 3251458N-(6-Methylpyridin-2-yl)pivalamideHCID 178527775HCID 178527775, compound

Product 1

HCID 69795730HCID 69795730, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a cold (ca. 0° C.) solution of 86.4 g (0.88 mole) of 2-amino-6-methylpyridine and 101 g (0.96 mole) of triethylamine in 1.0 liter of dichloromethane was added dropwise a solution of 106.1 g (0.88 mole) of trimethylacetyl chloride in 100 ml of dichloromethane. After stirring an hour after addition was completed, the mixture was poured into water and the layers separated. The aqueous layer was extracted with dichloromethane. The organic layers were combined and washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo to an oil that crystallized upon standing. The solid was triturated with hexane and collected by filtration, giving 115 g of 2-(trimethylacetamido)-6-methylpyridine. A 22.6 g (0.12 mmole) portion of the amide derivative was suspended in 250 ml of carbon tetrachloride containing 22.9 g (0.12 mmole) of N-bromosuccinimide and 100 mg of 2,2′-azabisisobutyronitrile. The mixture was heated at reflux under a sun lamp for one hour, after which insolubles were removed by filtration. The filtrate was concentrated in vacuo to an oil consisting of a mixture of the 6-bromomethyl-2-(trimethylacetamido)pyridine and 6-dibromomethyl-2-(trimethylacetamido)pyridine derivatives. The crude mixture was heated at reflux for fifteen minutes with 11.7 g (78 mmole) of 2-mercaptobenzimidazole in 300 ml of isopropyl alcohol. Upon cooling, a precipitate formed and was collected and washed with portions of isopropyl alcohol and diethylether. The trimethylacetyl group was removed by heating at reflux for four hours in 300 ml of 10% aqueous hydrochloric acid. After cooling, the mixture was concentrated in vacuo to an oil. The oil was dissolved in water and made alkaline with aqueous potassium carbonate. The oil that separated solidified upon addition of dichloromethane to the aqueous mixture. The solid was collected by filtration, washed with portions of water and dichloromethane, and air dried to yield 9.6 g of the title compound as an analytically pure hemihydrate. (An additional 2.5 g of the title compound was isolated from the dichloromethane washes.) Structure assignment was supported by the nmr and infrared spectra and by elemental analysis. Analysis. Calc'd. for C13H12N4S*½H2O: C, 58.84; H,4.93; N, 21.11; S, 12.08. Found: C, 59.03; H, 4.40; N, 20.90; S, 12.30.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux under a sun lamp for one hour
  3. customafter which insolubles were removed by filtration
  4. concentrationThe filtrate was concentrated in vacuo to an oil
  5. additionconsisting of a mixture of the 6-bromomethyl-2-(trimethylacetamido)pyridine and 6-dibromomethyl-2-(trimethylacetamido)pyridine derivatives
  6. temperatureThe crude mixture was heated
  7. temperatureUpon cooling
  8. customa precipitate formed
  9. customwas collected
  10. washwashed with portions of isopropyl alcohol and diethylether
  11. customThe trimethylacetyl group was removed
  12. temperatureby heating
  13. temperatureat reflux for four hours in 300 ml of 10% aqueous hydrochloric acid
  14. temperatureAfter cooling
  15. concentrationthe mixture was concentrated in vacuo to an oil
  16. dissolutionThe oil was dissolved in water
  17. customThe oil that separated
  18. additionsolidified upon addition of dichloromethane to the aqueous mixture
  19. filtrationThe solid was collected by filtration
  20. washwashed with portions of water and dichloromethane, and air
  21. customdried

Sources & evidence

ORD record
ord-5c69c68b4cc34f73a7616c89503eaaaa
Source dataset
uspto-grants-2005_06
Patent number
US06906078B2

Reaction notes

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