Pyridine → HCID 67483235, compound

HRID 398709Notes

Reaction equation

HRID 398709 reaction equation
[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[C:13]([C:21]([F:24])([F:23])[F:22])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:31][C:32]1[CH:37]=[CH:36][N:35]=[CH:34][N:33]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C)C=O.O1CCCC1>[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:18])=[O:19])=[C:13]([C:21]([F:22])([F:24])[F:23])[CH:12]=2)[C:8]([NH:31][C:32]2[CH:37]=[CH:36][N:35]=[CH:34][N:33]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 65578Oxalyl chlorideHCID 689584-AminopyrimidineHCID 21356243HCID 21356243, compound

Product 1

HCID 67483235HCID 67483235, compoundYield 336.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-propionic acid (8.32 g, 20.0 mmol) in methylene chloride (100 mL) cooled to 0° C. was treated with a 2.0M solution of oxalyl chloride in methylene chloride (11.14 mL, 22.28 mmol) and N,N-dimethylformamide (0.5 mL). The reaction mixture was stirred at 0° C. for 45 min and at 25° C. for 1 h. The reaction mixture was then cooled to 0° C. and treated with a solution of 4-aminopyrimidine (4.02 g, 4.28 mmol) in tetrahydrofuran (60 mL) followed by pyridine (6.0 mL, 74.2 mmol). This solution was stirred at 0° C. for 15 min and at 25° C. for 16 h. At this time, the reaction was poured onto a slurry of ice water (100 g) and then extracted with ethyl acetate (3×250 mL) and ether (1×200 mL). The combined organic layers were washed with water (1×500 mL) and a saturated aqueous sodium chloride solution (3×300 mL). The organic layer was then dried over sodium sulfate and magnesium sulfate, treated with charcoal, filtered through a pad of celite, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate) afforded 3-cyclopentyl-2(R)-(4-methanesulfonyl-3-trifluoromethyl-phenyl)-N-pyrimidin-4-yl-propionamide (6.36 g, 72.1%) as a white solid: mp 85-90° C.; [α]23589=−32.53° (c=0.166, chloroform); EI-HRMS m/e calcd for C20H22F3N3O3S (M+) 441.1334, found 441.1333.

Workup

  1. temperatureThe reaction mixture was then cooled to 0° C.
  2. stirringThis solution was stirred at 0° C. for 15 min and at 25° C. for 16 h
  3. extractionextracted with ethyl acetate (3×250 mL) and ether (1×200 mL)
  4. washThe combined organic layers were washed with water (1×500 mL)
  5. dry with materialThe organic layer was then dried over sodium sulfate and magnesium sulfate
  6. additiontreated with charcoal
  7. filtrationfiltered through a pad of celite
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3f476fb991a64dd48b44d9fc0bf3ca24
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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