Diisopropylethylamine → HCID 10074262, compound

HRID 719867Notes

Reaction equation

HRID 719867 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.[CH3:29][N:30]([CH3:34])[CH2:31][C:32]#[CH:33].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:33]#[C:32][CH2:31][N:30]([CH3:34])[CH3:29])=[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 81531DiisopropylethylamineHCID 81643N,N-DimethylpropargylamineHCID 86593779N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

Product 1

HCID 10074262HCID 10074262, compoundYield 74%

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, 1.0 mmol) and 1-dimethylamino-2-propyne (830 mg, 10.0 mmol) in toluene (6 ml) was treated with N,N-diisopropylethylamine (1.5 ml), copper(I) iodide (19.2 mg, 0.10 mmol), and dichlorobis(triphenylphosphine)palladium(II) (36.0 mg, 0.05 mmol). The resulting reaction mixture was stirred at 25° C. for 24 h. At this time, the reaction mixture was concentrated in vacuo. The residue was extracted into methylene chloride from water. The combined organic layers were dried and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 4/1 ethyl acetate/methanol) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-dimethylamino-prop-1-ynyl)-pyrazin-2-yl]-propionamide (360 mg, 74%) as a pale brown solid: (ES)+-HRMS m/e calcd for C24H29ClN4O3S (M+H)+ 489.1722, found 489.1725.

Workup

  1. customThe resulting reaction mixture
  2. concentrationAt this time, the reaction mixture was concentrated in vacuo
  3. extractionThe residue was extracted into methylene chloride from water
  4. customThe combined organic layers were dried
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c05201f707cd444a8d0de8eb5f05a431
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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