Methyl Isocyanate → 2-(3-Methylureido)-4-[4-(diphenylmethoxy)piperidinomethyl]thiazole

HRID 1649847Notes

Reaction equation

HRID 1649847 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([O:14][CH:15]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:10][CH2:9]2)[N:6]=1.[CH3:28][N:29]=[C:30]=[O:31].[OH-].[Na+]>O1CCCC1>[CH3:28][NH:29][C:30](=[O:31])[NH:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7][N:8]2[CH2:13][CH2:12][CH:11]([O:14][CH:15]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH2:10][CH2:9]2)[N:6]=1

Participants

5

Reactant 3

HCID 12228Methyl IsocyanateHCID 14798Sodium HydroxideHCID 198549372-Amino-4-[4-(diphenylmethoxy)piperidinomethyl]thiazole

Product 1

HCID 145009012-(3-Methylureido)-4-[4-(diphenylmethoxy)piperidinomethyl]thiazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-amino-4-[4-(diphenylmethoxy)piperidinomethyl]thiazole (1.0 g) in dry tetrahydrofuran (10 ml) was added dropwise methyl isocyanate (0.34 ml) at ambient temperature. After the addition had been completed, the reaction mixture was stirred for 3 hours. 1N Sodium hydroxide solution (3 ml) was added thereto and stirring was continued for 30 minutes. The reaction mixture was concentrated under reduced pressure and the residue was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After removal of solvent, the residue was subjected to column chromatography on silica gel and eluted with a mixture of chloroform and methanol (20:1 V/V). The fractions containing the object compound were combined and concentrated under reduced pressure. The residue was triturated with 70% ethanol to give white powder. Recrystallization from 70% ethanol gave 2-(3-methylureido)-4-[4-(diphenylmethoxy)piperidinomethyl]thiazole (0.3 g).

Workup

  1. additionAfter the addition
  2. stirringstirring
  3. waitwas continued for 30 minutes
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. extractionthe residue was extracted with ethyl acetate
  6. washThe extract was washed with a saturated aqueous solution of sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. customAfter removal of solvent
  9. washeluted with a mixture of chloroform and methanol (20:1 V/V)
  10. additionThe fractions containing the object compound
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was triturated with 70% ethanol
  13. customto give white powder
  14. customRecrystallization from 70% ethanol

Sources & evidence

ORD record
ord-a68b5fc93212480e9732c0ce195339f9
Source dataset
uspto-grants-1990_05
Patent number
US04921887

Reaction notes

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