Sodium hydride → tert-Butyl-2-(6-((2-(acetylamino)-1,3-benzothiazol-4-yl)oxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenylcarbamate

HRID 857667Notes

Reaction equation

HRID 857667 reaction equation
[OH:1][C:2]1[C:7]2[N:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[S:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[C:17]([O:21][C:22](=[O:41])[NH:23][C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:39]=[C:38](Cl)[N:37]=[CH:36][N:35]=1)([CH3:20])([CH3:19])[CH3:18]>CN(C=O)C>[C:17]([O:21][C:22](=[O:41])[NH:23][C:24]1[CH:29]=[C:28]([C:30]([F:32])([F:31])[F:33])[CH:27]=[CH:26][C:25]=1[C:34]1[CH:39]=[C:38]([O:1][C:2]2[C:7]3[N:8]=[C:9]([NH:11][C:12](=[O:14])[CH3:13])[S:10][C:6]=3[CH:5]=[CH:4][CH:3]=2)[N:37]=[CH:36][N:35]=1)([CH3:20])([CH3:18])[CH3:19]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 540449Acetamide, N-(4-hydroxy-2-benzothiazolyl)-HCID 23577237Tert-butyl 2-(6-chloropyrimidin-4-yl)-5-(trifluoromethyl)phenylcarbamate

Product 1

HCID 11957782tert-Butyl-2-(6-((2-(acetylamino)-1,3-benzothiazol-4-yl)oxy)pyrimidin-4-yl)-5-(trifluoromethyl)phenylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(4-hydroxybenzo-thiazol-2-yl)-acetamide, (Example 144(c)), (96 g, 27 mmol) in DMF (200 mL) was added NaH (0.68 g, 28 mmol, 60% dispersion in oil, Aldrich) and the mixture was stirred at 0° C. for 15 min. [2-(6-Chloro-pyrimidin-4-yl)-5-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester, (Example 148(b)), (10 g, 26 mmol) was then added and the reaction mixture was allowed to warm to room temperature, and stirred for 4.5 h. The reaction mixture was quenched with H2O (200 mL) and poured into a solution containing 30% ethyl acetate/hexanes (500 mL) and 1 N NaOH (800 mL). A white precipitate which formed was filtered and the filtercake was washed with H2O (100 mL) and 10% EtOAc/hexanes (100 mL). The filtercake was dried in vacuum, redissolved in an acetone/methanol mixture and adsorbed on silica gel. Purification by silica gel chromatography (2:1 EtOAc/hexanes) afforded the product as a white crystalline solid. Mp: 194–195° C. MS (ESI, pos. ion) m/z: 546 (M+1).

Workup

  1. additionwas then added
  2. customThe reaction mixture was quenched with H2O (200 mL)
  3. additionpoured into a solution
  4. additioncontaining 30% ethyl acetate/hexanes (500 mL) and 1 N NaOH (800 mL)
  5. customA white precipitate which formed
  6. filtrationwas filtered
  7. washthe filtercake was washed with H2O (100 mL) and 10% EtOAc/hexanes (100 mL)
  8. customThe filtercake was dried in vacuum
  9. dissolutionredissolved in an acetone/methanol mixture
  10. customPurification by silica gel chromatography (2:1 EtOAc/hexanes)

Sources & evidence

ORD record
ord-cc005ca614574826ad810f74372b9e18
Source dataset
uspto-grants-2006_12
Patent number
US07144888B2

Reaction notes

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