2-Aminothiazole → 3-cyclopentyl-2-[4-(1H-indol-5-yl)-phenyl]-N-thiazol-2-yl-propionamide

HRID 1935217

Reaction equation

HRID 1935217 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH:28]1([CH2:33][CH:34]([C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:45]=[C:46]4[C:50](=[CH:51][CH:52]=3)[NH:49][CH:48]=[CH:47]4)=[CH:40][CH:39]=2)[C:35](O)=[O:36])[CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:53][C:54]1[S:55][CH:56]=[CH:57][N:58]=1>C(Cl)Cl>[CH:28]1([CH2:33][CH:34]([C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:45]=[C:46]4[C:50](=[CH:51][CH:52]=3)[NH:49][CH:48]=[CH:47]4)=[CH:40][CH:39]=2)[C:35]([NH:53][C:54]2[S:55][CH:56]=[CH:57][N:58]=2)=[O:36])[CH2:29][CH2:30][CH2:31][CH2:32]1

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 224679073-cyclopentyl-2-[4-(1H-indol-5-yl)-phenyl]-propionic acid

Product 1

HCID 224679263-cyclopentyl-2-[4-(1H-indol-5-yl)-phenyl]-N-thiazol-2-yl-propionamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (71 mg, 0.27 mmol) in methylene chloride (1.5 mL) was cooled to 0° C. and then slowly treated with N-bromosuccinimide (48 mg, 0.27 mmol). The reaction mixture was stirred at 0° C. for 25 min and then treated with 3-cyclopentyl-2-[4-(1H-indol-5-yl)-phenyl]-propionic acid (75 mg, 0.23 mmol). The resulting reaction mixture was stirred at 0° C. for 5 min and then allowed to warm to 25° C. where it was stirred for 30 min. The reaction mixture was then treated with 2-aminothiazole (50 mg, 0.50 mmol). The resulting reaction mixture was stirred at 25° C. for 5 d. The crude reaction mixture was then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 9/1 chloroform/methanol) to afford impure 3-cyclopentyl-2-[4-(1H-indol-5-yl)-phenyl]-N-thiazol-2-yl-propionamide. Repurification by flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/3 hexanes/ethyl acetate) afforded pure 3-cyclopentyl-2-[4-(1H-indol-5-yl)-phenyl]-N-thiazol-2-yl-propionamide (8 mg, 9%) as a white solid: mp 112-115° C.; EI-HRMS m/e calcd for C25H25N3OS (M+) 415.1718, found 415.1714.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at 0° C. for 5 min
  3. temperatureto warm to 25° C. where it
  4. stirringwas stirred for 30 min
  5. customThe resulting reaction mixture
  6. stirringwas stirred at 25° C. for 5 d
  7. customThe crude reaction mixture
  8. customwas then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 9/1 chloroform/methanol)

Sources & evidence

ORD record
ord-167b611ba9434611ba2871fa6dc80ea5
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Linked notes

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