Cesium carbonate → 1-[5-Benzyloxy-7-(4-methyl-pyridin-2-yl)-benzothiazol-2-yl]-3-ethyl-urea

HRID 447058Notes

Reaction equation

HRID 447058 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11](Br)[C:12]2[S:16][C:15]([NH:17][C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[N:14][C:13]=2[CH:23]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[K+].Br[C:31]1[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][N:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.C(OC(=O)C)C>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:31]2[CH:36]=[C:35]([CH3:37])[CH:34]=[CH:33][N:32]=2)[C:12]2[S:16][C:15]([NH:17][C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[N:14][C:13]=2[CH:23]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 517044Potassium AcetateHCID 27340872-Bromo-4-methylpyridineHCID 578136291-(5-Benzyloxy-7-bromo-benzothiazol-2-yl)-3-ethyl-urea

Product 1

HCID 578135601-[5-Benzyloxy-7-(4-methyl-pyridin-2-yl)-benzothiazol-2-yl]-3-ethyl-urea

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-[5-Benzyloxy-7-bromo-benzothiazol-2-yl]-3-ethyl-urea (406 mg, 1.0 mmol), bis(neopentyl)glycolato diboron (452 mg, 2.0 mmol) and potassium acetate (294 mg, 3.0 mmol) in dimethyl sulfoxide (7 ml) was purged with nitrogen for 5 minutes. Bis(diphenylphosphino)ferrocene palladium(II)chloride complex (82 mg, 0.1 mmol) was added, the reaction mixture sealed and heated at 80° C. for 16 h. The reaction mixture was cooled to ambient temperature. 2-Bromo-4-methylpyridine (258 mg, 1.5 mmol) was added followed by aqueous cesium carbonate solution (3.7M, 0.405 ml, 1.5 mmol). The reaction mixture was purged with nitrogen for 5 minutes, treated with tetrakistriphenylphosphine palladium (0) (115 mg, 0.1 mmol), sealed and heated at 80° C. for 8 h. The reaction mixture was cooled to ambient temperature, diluted with ethylacetate (150 ml), washed with water (3×20 ml) followed by brine (25 ml) and dried (MgSO4). The solvent was removed in vacuo and the residue purified by flash silica chromatography eluting with 1:1 ethyl acetate:petrol ether to give 1-[5-Benzyloxy-7-(4-methyl-pyridin-2-yl)-benzothiazol-2-yl]-3-ethyl-urea as an off white solid (290 mg, 69%).

Workup

  1. customwas purged with nitrogen for 5 minutes
  2. additionBis(diphenylphosphino)ferrocene palladium(II)chloride complex (82 mg, 0.1 mmol) was added
  3. customthe reaction mixture sealed
  4. temperatureThe reaction mixture was cooled to ambient temperature
  5. customThe reaction mixture was purged with nitrogen for 5 minutes
  6. customsealed
  7. temperatureheated at 80° C. for 8 h
  8. temperatureThe reaction mixture was cooled to ambient temperature
  9. washwashed with water (3×20 ml)
  10. dry with materialdried (MgSO4)
  11. customThe solvent was removed in vacuo
  12. customthe residue purified by flash silica chromatography
  13. washeluting with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-29ddbd0e0bff43aa9b96646826cb0831
Source dataset
uspto-grants-2013_07
Patent number
US08481544B2

Reaction notes

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