Pyridine → HCID 178504751, compound

HRID 398692Notes

Reaction equation

HRID 398692 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.[NH:28]1[CH:35]=[CH:34][C:32]([NH2:33])=[N:31][C:29]1=[O:30].N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.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:33][C:32]2[CH:34]=[CH:35][NH:28][C:29](=[O:30])[N:31]=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 12067655(R)-2-(3-Chloro-4-(methylsulfonyl)phenyl)-3-cyclopentylpropanoic acidHCID 178418229Cytosine

Product 1

HCID 178504751HCID 178504751, compoundYield 57%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

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 (4 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 resulting reaction mixture was then treated with a solution of cytosine (101 mg, 0.91 mmol) and pyridine (0.245 mL, 3.03 mmol) in N,N-dimethylformamide (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 ethyl acetate (3×15 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 95/5 methylene chloride/methanol) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(2-oxo-1,2-dihydro-pyrimidin-4-yl)-propionamide (145 mg, 57%) as a white solid: mp >200° C.; EI-HRMS m/e calcd for C19H22ClN3O4S (M+) 423.1019, found 423.1015.

Workup

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

Sources & evidence

ORD record
ord-f82c6b0248bb467082e5b2e60c7398f8
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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