Formaldehyde → 1-[5-Bromo-6-hydroxy-7-(morpholinomethyl)-1,3-benzothiazol-2-yl]-3-ethyl-urea

HRID 1399974Notes

Reaction equation

HRID 1399974 reaction equation
C=O.[NH:3]1[CH2:8][CH2:7][O:6][CH2:5][CH2:4]1.[Br:9][C:10]1[C:11]([O:25]C)=[CH:12][C:13]2[S:17][C:16]([NH:18][C:19]([NH:21][CH2:22][CH3:23])=[O:20])=[N:15][C:14]=2[CH:24]=1.[CH3:27]COC(C)=O>CN(C=O)C.O>[Br:9][C:10]1[C:11]([OH:25])=[C:12]([CH2:27][N:3]2[CH2:8][CH2:7][O:6][CH2:5][CH2:4]2)[C:13]2[S:17][C:16]([NH:18][C:19]([NH:21][CH2:22][CH3:23])=[O:20])=[N:15][C:14]=2[CH:24]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 8083MorpholineHCID 8857Ethyl AcetateHCID 596030851-(5-Bromo-6-methoxy-1,3-benzothiazol-2-yl)-3-ethyl-urea

Product 1

HCID 866968941-[5-Bromo-6-hydroxy-7-(morpholinomethyl)-1,3-benzothiazol-2-yl]-3-ethyl-ureaYield 11%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Paraformaldehyde (29 mg, 0.05 mmol) was suspended in anhydrous DMF (2 mL) under argon and morpholine (0.08 mL, 0.95 mmol) added. The mixture was stirred at RT for 10 min then Intermediate 6 (200 mg, 0.63 mmol) added. The mixture was stirred at RT overnight, heated to 90° C. for 2 h then cooled to RT. The mixture was diluted with H2O and a precipitate formed. EtOAc was added but the precipitate remained insoluble. The suspension was filtered through a PTFE filter and the solid rinsed with H2O and EtOAc. The biphasic filtrate was extracted into EtOAc (4×20 mL). The combined organic layers were washed with H2O (3×50 mL), dried (Na2SO4) and concentrated in vacuo. The material was purified by chromatography, on silica eluting with 0-10% MeOH in DCM to give Intermediate 12 (28 mg, 11%).

Workup

  1. stirringThe mixture was stirred at RT overnight
  2. temperatureheated to 90° C. for 2 h
  3. temperaturethen cooled to RT
  4. customa precipitate formed
  5. filtrationThe suspension was filtered through a PTFE
  6. filtrationfilter
  7. washthe solid rinsed with H2O and EtOAc
  8. extractionThe biphasic filtrate was extracted into EtOAc (4×20 mL)
  9. washThe combined organic layers were washed with H2O (3×50 mL)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated in vacuo
  12. customThe material was purified by chromatography, on silica eluting with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-2507912c839e40edb7768dfd98ea6638
Source dataset
uspto-grants-2014_12
Patent number
US08906902B2

Reaction notes

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