Propargyl alcohol → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide

HRID 719866Notes

Reaction equation

HRID 719866 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([NH:8][C:9](=[O:28])[C@@H:10]([C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[C:19]([Cl:27])[CH:18]=2)[CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[N:6][CH:7]=1.[CH2:29]([OH:32])[C:30]#[CH:31].C(N(CC)C(C)C)(C)C>C1(C)C=CC=CC=1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:27][C:19]1[CH:18]=[C:17]([C@@H:10]([CH2:11][CH:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[C:9]([NH:8][C:5]2[CH:4]=[N:3][C:2]([C:31]#[C:30][CH2:29][OH:32])=[CH:7][N:6]=2)=[O:28])[CH:22]=[CH:21][C:20]=1[S:23]([CH3:26])(=[O:25])=[O:24]

Participants

7

Reactant 3

HCID 7859Propargyl alcoholHCID 81531DiisopropylethylamineHCID 86593779N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Product 1

HCID 104119922(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-prop-1-ynyl)-pyrazin-2-yl]-propionamideYield 59.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (prepared as in Example 6, 486 mg, 1 mmol) and propargyl alcohol (84 mg, 1.5 mmol) in toluene (6 mL) was treated with copper(I) iodide (19.2 mg, 0.10 mmol), dichlorobis(triphenylphosphine)palladium(II) (36 mg, 0.05 mmol), and N,N-diisopropylethylamine (2 ml). The resulting mixture was stirred at 25° C. for 1 h and was then heated to 60° C. for 1 h. At this time, the reaction was concentrated in vacuo. The residue was extracted into ethyl acetate from a 1N aqueous hydrochloric acid solution. The combined organic layers were washed with a saturated aqueous sodium chloride solution, dried, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 1/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-prop-1-ynyl)-pyrazin-2-yl]-propionamide (275 mg, 57%) as a pale yellow solid: (ES)+-HRMS m/e calcd for C22H24ClN3O4S (M+H)+ 462.1249, found 462.1252.

Workup

  1. temperaturewas then heated to 60° C. for 1 h
  2. concentrationAt this time, the reaction was concentrated in vacuo
  3. extractionThe residue was extracted into ethyl acetate from a 1N aqueous hydrochloric acid solution
  4. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution
  5. customdried
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-89cb8556e5bc4d90bc8ac2b3e71988a9
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

Loading…