Pyridine → HCID 59086447, compound

HRID 398686Notes

Reaction equation

HRID 398686 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][N:32]=[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][N:32]=[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 689584-AminopyrimidineHCID 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acid

Product 1

HCID 59086447HCID 59086447, compoundYield 42.2%

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 137, 200 mg, 0.61 mmol) in methylene chloride (5 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 (0.45 mL, 0.91 mmol) and stirred at 0° C. for 30 min. The reaction mixture was then treated with a solution of 4-aminopyrimidine (115 mg, 1.21 mmol) and pyridine (0.245 mL, 3.03 mmol) in tetrahydrofuran (10 mL). The resulting reaction mixture was allowed to warm to 25° C. where it was stirred for 16 h. The reaction mixture was then diluted with water (10 mL) and extracted with methylene chloride (3×15 mL). The combine organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 20/80 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-pyrimidin-4-yl-propionamide (105 mg, 43%, 80% R-isomer) as a white foam: [α]23589=−38.0° (c=0.050, chloroform); EI-HRMS m/e calcd for C19H22ClN3O3S (M+) 407.1070, found 407.1072.

Workup

  1. customThe resulting reaction mixture
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 16 h
  4. extractionextracted with methylene chloride (3×15 mL)
  5. dry with materialThe combine organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-47fe94866a7745129a9ada9b2821c329
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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