Water → N-tert-butyl-2-{1-[4-(4-chloro-phenyl)-6-methyl-pyrimidin-2-yl]-1H-imidazol-4-yl}-thiazole-5-sulfonamide

HRID 1928211Notes

Reaction equation

HRID 1928211 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[C:10]([N:15]3[CH:19]=[C:18]([Sn](CCCC)(CCCC)CCCC)[N:17]=[CH:16]3)[N:9]=2)=[CH:4][CH:3]=1.[C:33]([NH:37][S:38]([C:41]1[S:45][C:44](Cl)=[N:43][CH:42]=1)(=[O:40])=[O:39])([CH3:36])([CH3:35])[CH3:34].[F-].[K+].O>C1(C)C=CC=CC=1>[C:33]([NH:37][S:38]([C:41]1[S:45][C:44]([C:18]2[N:17]=[CH:16][N:15]([C:10]3[N:9]=[C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[CH:13]=[C:12]([CH3:14])[N:11]=3)[CH:19]=2)=[N:43][CH:42]=1)(=[O:39])=[O:40])([CH3:36])([CH3:34])[CH3:35]

Participants

6

Reactant 4

HCID 962WaterHCID 522689Potassium FluorideHCID 434557712-Chloro-thiazole-5-sulfonic acid tert-butylamideHCID 574688274-(4-Chloro-phenyl)-6-methyl-2-(4-tributylstannanyl-imidazol-1-yl)-pyrimidine

Product 1

HCID 57468959N-tert-butyl-2-{1-[4-(4-chloro-phenyl)-6-methyl-pyrimidin-2-yl]-1H-imidazol-4-yl}-thiazole-5-sulfonamideYield 25.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A stirred mixture of 4-(4-chloro-phenyl)-6-methyl-2-(4-tributylstannanyl-imidazol-1-yl)-pyrimidine (Example G.3) (0.45 g, 0.80 mmol), 2-chloro-thiazole-5-sulfonic acid tert-butylamide (Example H.1) (0.225 g, 0.88 mmol), tetrakis(triphenyl-phosphine)palladium (0.056 g, 0.048 mmol) in toluene (10 mL) was heated under reflux conditions for 15 h. The mixture was poured into saturated potassium fluoride solution (10 mL), water (40 mL) was added and the water layer was extracted with ethyl acetate (2×60 mL). The combined organic layers were washed with brine (60 mL), dried (MgSO4) and evaporated. The crude product was purified by flash chromatography (heptane/ethyl acetate) and crystallization (THF/hexane) to yield N-tert-butyl-2-{1-[4-(4-chloro-phenyl)-6-methyl-pyrimidin-2-yl]-1H-imidazol-4-yl}-thiazole-5-sulfonamide (0.1 g) as a light brown solid.

Workup

  1. temperaturewas heated under reflux conditions for 15 h
  2. additionwas added
  3. extractionthe water layer was extracted with ethyl acetate (2×60 mL)
  4. washThe combined organic layers were washed with brine (60 mL)
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe crude product was purified by flash chromatography (heptane/ethyl acetate) and crystallization (THF/hexane)

Sources & evidence

ORD record
ord-6affcc11cb9a4af6af97ee9c3d35471c
Source dataset
uspto-grants-2012_05
Patent number
US08183262B2

Reaction notes

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