2-Aminopyridine → HCID 10177246, compound

HRID 1935261Notes

Reaction equation

HRID 1935261 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:49]=[CH:48][N:47]=[CH:46][CH:45]=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[CH:56]=[CH:55][CH:54]=[CH:53][N:52]=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]=[CH:46][N:47]=[CH:48][CH:49]=3)=[CH:40][CH:39]=2)[C:35]([NH:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][N:52]=2)=[O:37])[CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 104392-AminopyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 22467912HCID 22467912, compound

Product 1

HCID 10177246HCID 10177246, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (59 mg, 0.22 mmol) in methylene chloride (1 mL) was cooled to 0° C. and then slowly treated with N-bromosuccinimide (39 mg, 0.22 mmol). The reaction mixture was stirred at 0° C. for 20 min and then treated with 3-cyclopentyl-2-(4-pyridin-4-yl-phenyl)-propionic acid (55 mg, 0.19 mmol). The resulting reaction mixture was stirred at 0° C. for 10 min and then allowed to warm to 25° C., where it was stirred for 20 min. The reaction mixture was then treated with 2-aminopyridine (39 mg, 0.41 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, 20/1 methylene chloride/methanol) to afford impure 3-cyclopentyl-N-pyridin-2-yl-2-(4-pyridin-4-yl-phenyl)-propionamide as a yellow solid. Repurification by flash chromatography (Merck Silica gel 60, 230-400 mesh, 100% ethyl acetate) afforded pure 3-cyclopentyl-2-(4-pyridin-4-yl-phenyl)-N-thiazol-2-yl-propionamide (10 mg, 14%) as a yellow solid: mp 165-167° C.; EI-HRMS m/e calcd for C24H25N3O (M+) 371.1998, found 371.1998.

Workup

  1. customThe resulting reaction mixture
  2. stirringwas stirred at 0° C. for 10 min
  3. temperatureto warm to 25° C.
  4. stirringwhere it was stirred for 20 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, 20/1 methylene chloride/methanol)

Sources & evidence

ORD record
ord-8a18439cfb5f44489bc70d4cc7a40a85
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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