2-Aminothiazole → HCID 9884201, compound

HRID 276170Notes

Reaction equation

HRID 276170 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH3:28][S:29]([C:32]1[CH:37]=[CH:36][C:35](/[C:38](=[CH:42]\[CH2:43][CH3:44])/[C:39]([OH:41])=O)=[CH:34][CH:33]=1)(=[O:31])=[O:30].[NH2:45][C:46]1[S:47][CH:48]=[CH:49][N:50]=1>C(Cl)Cl>[S:47]1[CH:48]=[CH:49][N:50]=[C:46]1[NH:45][C:39](=[O:41])/[C:38](/[C:35]1[CH:34]=[CH:33][C:32]([S:29]([CH3:28])(=[O:30])=[O:31])=[CH:37][CH:36]=1)=[CH:42]/[CH2:43][CH3:44]

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 67483058HCID 67483058, compound

Product 1

HCID 9884201HCID 9884201, compoundYield 16.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (1.23 g, 4.7 mmol) in methylene chloride (15 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (836 mg, 4.7 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of (E)-2-(4-(methanesulfonyl)-phenyl)-pentenoic acid (703 mg, 2.76 mmol) in methylene chloride (5 mL). The clear solution was stirred for 10 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 1.5 h. The reaction mixture was then treated with 2-aminothiazole (829 mg, 8.28 mmol), and the resulting suspension was stirred for 15 h at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (100 mL) and a 1N aqueous hydrochloric acid solution (100 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×50 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (2×50 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 4/1 to 1/1 hexanes/ethyl acetate) afforded (E)-2-(4-methanesulfonyl-phenyl)-pent-2-enoic acid thiazol-2-ylamide (150 mg, 16%) as crystalline solid: mp 155-158° C.; EI-HRMS m/e calcd for C15H16N2O3S2 (M+) 336.0602, found 336.0601.

Workup

  1. stirringThe clear solution was stirred for 10 min at 0° C.
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 1.5 h
  4. stirringthe resulting suspension was stirred for 15 h at 25° C
  5. concentrationThe reaction mixture was then concentrated in vacuo
  6. customto remove methylene chloride
  7. additionthe residue was diluted with ethyl acetate (100 mL)
  8. customThe two layers were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (1×50 mL)
  10. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (2×50 mL)
  11. dry with materiala saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-40628ece62cb4357a8a1daf6290ffe67
Source dataset
uspto-grants-2002_03
Patent number
US06353111B1

Reaction notes

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