2-Aminothiazole → HCID 10158899, compound

HRID 1936347Notes

Reaction equation

HRID 1936347 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]([CH:41]([CH2:45][CH:46]2[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.[NH2:51][C:52]1[S:53][CH:54]=[CH:55][N:56]=1>C(Cl)Cl>[Cl:28][C:29]1[CH:30]=[C:31]([CH:41]([CH2:45][CH:46]2[CH2:47][CH2:48][CH2:49][CH2:50]2)[C:42]([NH:51][C:52]2[S:53][CH:54]=[CH:55][N:56]=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 11209847HCID 11209847, compound

Product 1

HCID 10158899HCID 10158899, compoundYield 42.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (236 mg, 0.9 mmol) in methylene chloride (6 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (160 mg, 0.9 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with the 2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cyclopentyl-propionic acid (151 mg, 0.45 mmol). The clear solution was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 2 h. The reaction mixture was then treated with 2-aminothiazole (135 mg, 1.35 mmol), and the resulting suspension was stirred for 20 h at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (30 mL) and a 1N aqueous hydrochloric acid solution (30 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×20 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) afforded 2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cyclopentyl-N-thiazol-2-yl-propionamide (80 mg, 42%) as a white solid: mp 190-193° C.; EI-HRMS m/e calcd for C19H21ClN6OS (M+) 416.1186, found 416.1183.

Workup

  1. stirringThe clear solution was stirred for 15 min at 0° C.
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 2 h
  4. stirringthe resulting suspension was stirred for 20 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 (30 mL)
  8. customThe two layers were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (1×20 mL)
  10. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL)
  11. dry with materiala saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a6ae6c044ab84164b9e596dd07bc62fa
Source dataset
uspto-grants-2002_05
Patent number
US06388088B1

Reaction notes

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