2-Aminoquinoline → HCID 10224075, compound

HRID 2306301Notes

Reaction equation

HRID 2306301 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.C(N(CC)C(C)C)(C)C.[NH2:36][C:37]1[CH:46]=[CH:45][C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[N:38]=1>C(Cl)Cl.CN(C)C=O.O1CCCC1>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([NH:36][C:37]2[CH:46]=[CH:45][C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[N:38]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 113792-AminoquinolineHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 120694893-Cyclopentyl-2-(4-methanesulfonyl-phenyl)propionic acid

Product 1

HCID 10224075HCID 10224075, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-propionic acid (prepared as in Example 12, 200 mg, 0.68 mmol) in methylene chloride (8 mL) was treated with dry N,N-dimethylformamide (1 drop). The reaction mixture was cooled to 0° C. and then treated dropwise with a 2M solution of oxalyl chloride in methylene chloride (0.38 mL, 0.78 mmol). The reaction mixture was stirred at 0° C. for 10 min and then stirred at 25° C. for 30 min. The reaction mixture was then treated with N,N-diisopropylethylamine (0.28 mL, 1.64 mmol) followed by a solution of 2-aminoquinoline (208 mg, 1.44 mmol) in dry tetrahydrofuran (1 mL). The resulting reaction mixture was stirred at 25° C. for 17 h. The reaction mixture was concentrated in vacuo. The resulting residue was adsorbed onto silica gel (Merck Silica gel 60, 230-400 mesh) and then purified via Biotage chromatography (FLASH 40S, Silica, 3/2 hexanes/ethyl acetate) to afford 3-cyclopentyl-2-(4-methanesulfonyl-phenyl)-N-quinolin-2-yl-propionamide (195 mg, 68%) as a white foam; EI-HRMS m/e calcd for C24H26N2O3S (M+) 422.1665, found 422.1664.

Workup

  1. stirringstirred at 25° C. for 30 min
  2. customThe resulting reaction mixture
  3. stirringwas stirred at 25° C. for 17 h
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. custompurified via Biotage chromatography (FLASH 40S, Silica, 3/2 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-046b38ccbd4c4c65b375e63a1235dcaf
Source dataset
uspto-grants-2002_08
Patent number
US06441184B1

Reaction notes

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