Pyridine → HCID 12069487, compound

HRID 1280014Notes

Reaction equation

HRID 1280014 reaction equation
[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[CH:35]=[CH:34][C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[N:27]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1.O>[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:25][C:26]2[CH:35]=[CH:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:27]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

9

Reactant 4

HCID 1049PyridineHCID 113792-AminoquinolineHCID 65578Oxalyl chlorideHCID 12069486(2R)-3-cyclopentyl-2-(3,4-dichloro-phenyl)-propionic acid

Product 1

HCID 12069487HCID 12069487, compoundYield 65%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-propionic acid (prepared as in Example 3, 100 mg, 0.35 mmol) in methylene chloride (2 mL) was treated with N,N-dimethylformamide (1 drop) and then cooled to 0° C. The reaction mixture was then treated dropwise with a 2M solution of oxalyl chloride in methylene chloride (0.26 mL, 0.52 mmol) and then stirred at 0° C. for 30 min. The resulting reaction mixture was then treated with a solution of 2-aminoquinoline (75 mg, 0.52 mmol) and pyridine (0.14 mL, 1.74 mmol) in tetrahydrofuran (5 mL), and the reaction mixture was allowed to warm to 25° C. The reaction was then stirred at 25° C. for 16 hours. The reaction mixture was 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, 90/10 hexanes/ethyl acetate) afforded 3-cyclopentyl-2(R)-(3,4-dichloro-phenyl)-N-quinolin-2-yl-propionamide (93 mg, 65%) as an oil: EI-HRMS m/e calcd for C23H22Cl2N2O (M+) 412.1109, found 412.1123.

Workup

  1. customThe resulting reaction mixture
  2. temperatureto warm to 25° C
  3. stirringThe reaction was then stirred at 25° C. for 16 hours
  4. extractionextracted with methylene chloride (3×15 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dcf5901fee434fb2bf71540cfeb19da6
Source dataset
uspto-grants-2002_09
Patent number
US06448399B1

Reaction notes

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