2-Aminothiazole → 3-cyclopentyl-2-(4-pyridin-3-yl-phenyl)-N-thiazol-2-yl-propionamide

HRID 1935207Notes

Reaction equation

HRID 1935207 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]=[N:46][CH:47]=[CH:48][CH:49]=3)=[CH:40][CH:39]=2)[C:35]([OH:37])=O)[CH2:32][CH2:31][CH2:30][CH2:29]1.[NH2:50][C:51]1[S:52][CH:53]=[CH:54][N:55]=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]=[N:46][CH:47]=[CH:48][CH:49]=3)=[CH:40][CH:39]=2)[C:35]([NH:50][C:51]2[S:52][CH:53]=[CH:54][N:55]=2)=[O:37])[CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 21552-AminothiazoleHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 224679003-Cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionic acid

Product 1

HCID 224679223-cyclopentyl-2-(4-pyridin-3-yl-phenyl)-N-thiazol-2-yl-propionamideYield 8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (160 mg, 0.61 mmol) in methylene chloride (4 mL) was cooled to 0° C. and then slowly treated with N-bromosuccinimide (109 mg, 0.61 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with 3-cyclopentyl-2-(4-pyridin-3-yl-phenyl)-propionic acid (150 mg, 0.51 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 (112 mg, 1.12 mmol). The resulting reaction mixture was stirred at 25° C. for 15 h. The crude reaction mixture was then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 100% diethyl ether then 1/1 diethyl ether/ethyl acetate then 1/3 diethyl ether/ethyl acetate) to afford 3-cyclopentyl-2-(4-pyridin-3-yl-phenyl)-N-thiazol-2-yl-propionamide (15 mg, 8%) as a pale yellow foam: mp 48-52° C.; EI-HRMS m/e calcd for C22H23N3OS (M+) 377.1562, found 377.1564.

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 15 h
  7. customThe crude reaction mixture
  8. customwas then directly purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 100% diethyl ether

Sources & evidence

ORD record
ord-148f0f46204c4ab1a078db0d2c06d6a2
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

Loading…