Water → HCID 178517656, compound

HRID 1027496Notes

Reaction equation

HRID 1027496 reaction equation
[C:1](Cl)(Cl)=[S:2].[NH2:5][C:6]1[C:7]([OH:21])=[N:8][C:9]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[N:10][C:11]=1[OH:12].C(=O)([O-])[O-].[K+].[K+].O>CN1CCCC1=O>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][C:9]2[N:8]=[C:7]([OH:21])[C:6]3[N:5]=[C:1]([SH:2])[O:12][C:11]=3[N:10]=2)=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10040ThiophosgeneHCID 11430Potassium CarbonateHCID 178508108HCID 178508108, compound

Product 1

HCID 178517656HCID 178517656, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
5 °C

Procedure

3 ml of thiophosgene were added slowly to a suspension of 9.65 g of 5-amino-2-(4-chloro-benzyl)-pyrimidine-4,6-diol and 5.3 g of potassium carbonate in 75 ml of N-methyl-pyrrolidin-2-one (NMP) while maintaining the temperature below 10° C. The reaction mixture was stirred for 2 h at 0-10° C. Then 300 ml of water were added and the resulting solution was extracted three times with 200 ml of dichloromethane and three times with 200 ml of a mixture of dichloromethane and isopropanol (3:1). The combined organic phases were dried over sodium sulfate and filtered. The solvents were removed in vacuo to yield approximately 7 g of 5-(4-chloro-benzyl)-2-mercapto-oxazolo[5,4-d]pyrimidin-7-ol as a solution in NMP. 45 ml of NMP and a solution of 2.38 g of sodium hydroxide in 64 ml of water were added at 0° C., and the mixture was stirred for 30 min at 0° C. while the color changed to brown. Then a solution of 1.5 ml of iodomethane in 1.5 ml of NMP was added dropwise. After stirring at 0° C. for 90 min the reaction was complete. The solution was extracted twice with 80 ml of ethyl acetate, and the combined organic phases were dried over sodium sulfate and filtered. The solvents were removed in vacuo to yield 2.2 g of the title compound as a brown solid.

Workup

  1. temperaturewhile maintaining the temperature below 10° C
  2. extractionthe resulting solution was extracted three times with 200 ml of dichloromethane and three times with 200 ml of a mixture of dichloromethane and isopropanol (3:1)
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. filtrationfiltered
  5. customThe solvents were removed in vacuo

Sources & evidence

ORD record
ord-3e15ff35d80e4a15b73d44c95db679f7
Source dataset
uspto-grants-2014_05
Patent number
US08735387B2

Reaction notes

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