Pyridine → HCID 67483081, compound

HRID 719857Notes

Reaction equation

HRID 719857 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C(Cl)(=O)C(Cl)=O.[NH2:28][C:29]1[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[CH:31][N:30]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[C:13]([NH:28][C:29]2[CH:34]=[CH:33][C:32]([C:35]#[N:36])=[CH:31][N:30]=2)=[O:15])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

9

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 8182602-Amino-5-cyanopyridineHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acid

Product 1

HCID 67483081HCID 67483081, compoundYield 86%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionic acid (prepared as in Example 1, 300 mg, 0.91 mmol) in methylene chloride (10 mL) and N,N-dimethylformamide (1 drop) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (0.52 mL, 1.04 mmol). The reaction was stirred at 0° C. for 30 min. At this time, the reaction was concentrated in vacuo to give a light yellow oil. The residue was then treated with a solution of 2-amino-5-cyanopyridine (216 mg, 1.80 mmol) in tetrahydrofuran (5 mL) and pyridine (0.37 mL, 4.5 mmol). The reaction was then stirred at 25° C. for 16 h. At this time, the reaction was diluted with water (15 mL) and extracted with methylene chloride (3×25 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 7/3 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-cyano-pyridin-2-yl)-3-cyclopentyl-propionamide (53 mg, 86%) as a colorless oil: (ES)+-HRMS m/e calcd for C21H22ClN3O3S (M+H)+ 432.1143, found 432.1147.

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo
  2. customto give a light yellow oil
  3. stirringThe reaction was then stirred at 25° C. for 16 h
  4. extractionextracted with methylene chloride (3×25 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c50670e87a0440829c4801b6c4c038a0
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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