2-Aminothiazole → HCID 10181905, compound

HRID 2306433Notes

Reaction equation

HRID 2306433 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Cl:28][C:29]1[CH:30]=[C:31](/[C:41](=[CH:45]\[CH:46]2[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)/[C:42](O)=[O:43])[CH:32]=[CH:33][C:34]=1[N:35]1[C:39]([CH3:40])=[N:38][N:37]=[N:36]1.[NH2:53][C:54]1[S:55][CH:56]=[CH:57][N:58]=1>C(Cl)Cl>[Cl:28][C:29]1[CH:30]=[C:31](/[C:41](=[CH:45]\[CH:46]2[CH2:52][CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)/[C:42]([NH:53][C:54]2[S:55][CH:56]=[CH:57][N:58]=2)=[O:43])[CH:32]=[CH:33][C:34]=1[N:35]1[C:39]([CH3:40])=[N:38][N:37]=[N:36]1

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 12019653HCID 12019653, compound

Product 1

HCID 10181905HCID 10181905, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (1.45 g, 5.54 mmol) in methylene chloride (15 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (986 mg, 5.54 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with a solution of (E)-2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cycloheptyl-acrylic acid (1.00 g, 2.77 mmol) in methylene chloride (5 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 (832 g, 8.32 mmol), and the resulting suspension was stirred for 3 d at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (50 mL) and water (50 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 (1×100 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, 1/1 hexanes/ethyl acetate) afforded (E)-2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cycloheptyl-N-thiazol-2-yl-acrylamide (810 mg, 66%) as an amorphous white solid: EI-HRMS m/e calcd for C21H23ClN6OS (M+) 442.1343, found 442.1343.

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 3 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 (50 mL) and water (50 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 (1×100 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-e6759de149364e2b93d105a935432767
Source dataset
uspto-grants-2002_08
Patent number
US06441180B1

Reaction notes

Loading…