Pyrrole → Urea

HRID 464916Notes

Reaction equation

HRID 464916 reaction equation
Cl[S:2]([N:5]=[C:6]=[O:7])(=[O:4])=[O:3].[NH2:8][C:9]1[N:14]=[C:13]([O:15][CH:16]([F:18])[F:17])[CH:12]=[C:11]([CH3:19])[N:10]=1.[NH:20]1[CH:24]=[CH:23][CH:22]=[CH:21]1>O1CCCC1>[NH2:5][C:6]([NH2:8])=[O:7].[NH:20]1[CH:24]=[CH:23][C:22]([S:2]([NH:5][C:6]([NH:8][C:9]2[N:14]=[C:13]([O:15][CH:16]([F:18])[F:17])[CH:12]=[C:11]([CH3:19])[N:10]=2)=[O:7])(=[O:4])=[O:3])=[CH:21]1

Participants

6

Reactant 3

HCID 8027PyrroleHCID 70918Chlorosulfonyl isocyanateHCID 28173904-(Difluoromethoxy)-6-methylpyrimidin-2-amine

Product 2

HCID 1176UreaHCID 20261268N-(3-pyrrolylsulfonyl)-N'-(4-difluoromethoxy-6-methylpyrimidin-2-yl)urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

5.7 g of chlorosulfonylisocyanate are added dropwise at 0°-5° C. to a solution of 7 g of 2-amino-4-difluoromethoxy-6-methylpyrimidine in 100 ml of absolute tetrahydrofuran. The yellowish solution is stirred for 10 minutes at 0° C., then 5.6 ml of pyrrole are added and the reaction mixture is stirred for 17 hours at 20°-25° C. The solvent is evaporated off and the residue is taken up in a mixture of 25 ml of methanol, 50 ml of water and 3.2 g of sodium hydroxide. The solution is shaken vigorously for 10 minutes, washed with two 50 ml portions of methylene chloride and acidified with glacial acetic acid. The acid aqueous solution is then extracted with ethyl acetate. The organic extracts are dried over magnesium sulfate and concentrated to give a 1:1 mixture of two isomers in 20% yield. This mixture of isomers is chromatographed over silica gel with a 4:1 mixture of petroleum ether/ethyl acetate, affording N-(2-pyrrolylsulfonyl)-N'-4-difluoromethoxy-6-methylpyrimidin-2-yl)urea with a melting point of 189° C. (compound 4.1) and N-(3-pyrrolylsulfonyl)-N'-(4-difluoromethoxy-6-methylpyrimidin-2-yl)urea with a melting point of 173°-174° C. (compound 4.8).

Workup

  1. stirringthe reaction mixture is stirred for 17 hours at 20°-25° C
  2. customThe solvent is evaporated off
  3. additionthe residue is taken up in a mixture of 25 ml of methanol, 50 ml of water and 3.2 g of sodium hydroxide
  4. stirringThe solution is shaken vigorously for 10 minutes
  5. washwashed with two 50 ml portions of methylene chloride
  6. extractionThe acid aqueous solution is then extracted with ethyl acetate
  7. dry with materialThe organic extracts are dried over magnesium sulfate
  8. concentrationconcentrated
  9. customto give
  10. additiona 1:1 mixture of two isomers in 20% yield
  11. additionThis mixture of isomers
  12. customis chromatographed over silica gel with a 4:1 mixture of petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-b4b188c0df794ed897f4fba016df1cc6
Source dataset
uspto-grants-1985_10
Patent number
US04549898

Reaction notes

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