Pyridine → HCID 10111883, compound

HRID 276220Notes

Reaction equation

HRID 276220 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:39](=[CH:43]\[CH:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)/[C:40]([OH:42])=O)[CH:32]=[CH:33][C:34]=1[S:35]([CH3:38])(=[O:37])=[O:36].[NH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][N:51]=1.N1C=CC=CC=1>C(Cl)Cl.O>[Cl:28][C:29]1[CH:30]=[C:31](/[C:39](=[CH:43]\[CH:44]2[CH2:48][CH2:47][CH2:46][CH2:45]2)/[C:40]([NH:49][C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][N:51]=2)=[O:42])[CH:32]=[CH:33][C:34]=1[S:35]([CH3:38])(=[O:36])=[O:37]

Participants

8

Reactant 5

HCID 1049PyridineHCID 104392-AminopyridineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 53348310HCID 53348310, compound

Product 1

HCID 10111883HCID 10111883, compoundYield 25.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (266 mg, 01.01 mmol) in methylene chloride (11 mL) was cooled to 0° C. and then slowly treated with N-bromosuccinimide (204 mg, 1.15 mmol). The reaction mixture was stirred at 0° C. until the reaction mixture became homogeneous. The resulting light purple reaction mixture was then treated with (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-acrylic acid (prepared in Example 9, 222 mg, 0.68 mmol), and the reaction mixture was stirred at 0° C. for 20 min. The reaction mixture was then allowed to warm to 25° C. where it was stirred for 30 min. After such time, the reaction mixture was treated with 2-aminopyridine (95 mg, 1.01 mmol) and pyridine (0.098 mL, 1.22 mmol), and the resulting reaction mixture was stirred at 25° C. for 16 h. The reaction was then diluted with water (10 mL) and extracted with methylene chloride (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 75/25 hexanes/ethyl acetate) afforded (E)-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyridin-2-yl-acrylamide (70 mg, 25%) as a yellow glassy solid: EI-HRMS m/e calcd for C20H21ClN2O3S (M+) 404.0961, found 404.0962.

Workup

  1. stirringthe reaction mixture was stirred at 0° C. for 20 min
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 30 min
  4. customthe resulting reaction mixture
  5. stirringwas stirred at 25° C. for 16 h
  6. extractionextracted with methylene chloride (3×15 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0e29bcfd705242a0b1664fce5df4a943
Source dataset
uspto-grants-2002_03
Patent number
US06353111B1

Reaction notes

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