2-Aminothiazole → HCID 10115152, compound

HRID 276201Notes

Reaction equation

HRID 276201 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1(/[CH:33]=[C:34](\[C:38]2[CH:43]=[CH:42][C:41]([S:44]([CH3:47])(=[O:46])=[O:45])=[C:40]([Br:48])[CH:39]=2)/[C:35]([OH:37])=O)[CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:49][C:50]1[S:51][CH:52]=[CH:53][N:54]=1>C(Cl)Cl>[Br:48][C:40]1[CH:39]=[C:38](/[C:34](=[CH:33]\[CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32]2)/[C:35]([NH:49][C:50]2[S:51][CH:52]=[CH:53][N:54]=2)=[O:37])[CH:43]=[CH:42][C:41]=1[S:44]([CH3:47])(=[O:46])=[O:45]

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 67483012HCID 67483012, compound

Product 1

HCID 10115152HCID 10115152, compoundYield 17.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (467 mg, 1.78 mmol) in methylene chloride (8 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (317 mg, 1.78 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution (E)-3-cyclopentyl-2-[3-bromo-4-(methanesulfonyl)-phenyl]-acrylic acid (334 mg, 0.89 mmol) in methylene chloride (4 mL). The reaction mixture was stirred for 15 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 (713 mg, 7.12 mmol), and the resulting suspension was stirred for 2 d at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (40 mL) and a 1N aqueous hydrochloric acid solution (50 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×25 mL). The combined organic extracts were successively washed with a 1N aqueous hydrochloric acid solution (1×50 mL), a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotaoe chromatography (FLASH 40S, Silica, 3/1 hexanes/ethyl acetate) afforded the pure (E)-2-(3-bromo-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-thiazol-2-yl-acrylamide (71 mg, 17.5%) as an amorphous white solid: EI-HRMS m/e calcd for C18H19BrN2O3S2 (M+) 454.0020, found 454.0025.

Workup

  1. stirringThe reaction mixture was stirred for 15 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 2 d 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 (40 mL)
  8. customThe two layers were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (1×25 mL)
  10. washThe combined organic extracts were successively washed with a 1N aqueous hydrochloric acid solution (1×50 mL)
  11. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1d979bda967a464185d2069c81b370a8
Source dataset
uspto-grants-2002_03
Patent number
US06353111B1

Reaction notes

Loading…