Water → 1-(2-Chloro-6-methylphenyl)-3-cyclobutyltetrahydro-2(1H)-pyrimidinethione

HRID 1250902Notes

Reaction equation

HRID 1250902 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][CH2:9][CH2:10][CH2:11][NH:12][CH:13]2[CH2:16][CH2:15][CH2:14]2)=[C:6]([CH3:17])[CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:25](Cl)(Cl)=[S:26].O>C(Cl)(Cl)Cl>[Cl:1][C:2]1[C:7]([N:8]2[CH2:9][CH2:10][CH2:11][N:12]([CH:13]3[CH2:16][CH2:15][CH2:14]3)[C:25]2=[S:26])=[C:6]([CH3:17])[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 10040ThiophosgeneHCID 18324820HCID 18324820, compound

Product 1

HCID 99261531-(2-Chloro-6-methylphenyl)-3-cyclobutyltetrahydro-2(1H)-pyrimidinethioneYield 81%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of the diamine of Step A (3.28 g) in dry chloroform (48 mL) was added dropwise under nitrogen at 0° C. triethylamine (3.62 mL). Thiophosgene (1.49 mL) was then added dropwise via syringe and the mixture was stirred in the cold for another 15 minutes. Stirring was continued at room temperature for 1.5 hours, water was added and the the pH was adjusted to 8 with triethylamine. The aqueous layer was further extracted with dichloromethane and the combined extracts were washed with 20% aqueous sodium chloride, dried over anhydrous potasium carbonate and evaporated to dryness. The residue was dissolved in dichloromethane and absorbed onto a column of Merck-60 flash silica gel. Elution with hexane-ethyl acetate 9:1 provided the title compound (3.1 g, 81%) which was further triturated and sonicated with hexane and hexane-ether. The off-white solid was collected, washed with hexane and dried (2.69 g, 75.3%), m.p. 89-91° C.

Workup

  1. stirringStirring
  2. waitwas continued at room temperature for 1.5 hours
  3. extractionThe aqueous layer was further extracted with dichloromethane
  4. washthe combined extracts were washed with 20% aqueous sodium chloride
  5. dry with materialdried over anhydrous potasium carbonate
  6. customevaporated to dryness
  7. dissolutionThe residue was dissolved in dichloromethane
  8. customabsorbed onto a column of Merck-60 flash silica gel
  9. washElution with hexane-ethyl acetate 9:1

Sources & evidence

ORD record
ord-fb5b9ce4f6ef4b108429f3bd9066c9f6
Source dataset
uspto-grants-2002_01
Patent number
US06340687B1

Reaction notes

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