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2-Methyl-3-butyn-2-ol → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-3-methyl-but-1-ynyl)-pyrazin-2-yl]-propionamide

HRID 719952
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HRID 719952 반응식
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.C(N(CC)C(C)C)(C)C.[OH:38][C:39]([CH3:43])([CH3:42])[C:40]#[CH:41]>C1(C)C=CC=CC=1.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.[Cu]I>[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:41]#[C:40][C:39]([OH:38])([CH3:43])[CH3:42])=[CH:7][N:6]=2)=[O:28])[CH:22]=[CH:21][C:20]=1[S:23]([CH3:26])(=[O:25])=[O:24]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 3

HCID 82582-Methyl-3-butyn-2-olHCID 81531DiisopropylethylamineHCID 86593779N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide

생성물 1

HCID 99830242(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-3-methyl-but-1-ynyl)-pyrazin-2-yl]-propionamide수율 84.1%

시약·촉매·용매 3

HCID 24350
Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)
촉매
HCID 178418476HCID 178418476, 화합물촉매
HCID 1140Toluene용매

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온도
25 °C

실험 절차

A suspension 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) in toluene (8 mL) was treated with N,N-diisopropylethylamine (2 mL), 3-hydroxy-3-methylbutyne (168 mg, 2.0 mmol), dichlorobis(triphenylphosphine)palladium(II) (40 mg), and copper(I) iodide (20 mg). The mixture was stirred at 25° C. overnight, and an oily black precipitate was obtained. The top clear solution was decanted, and the oily precipitate was rinsed first with toluene (5 mL) and then with hexanes (5 mL). The residue was dissolved in methylene chloride and extracted with methylene chloride and a 0.2N aqueous hydrochloric acid solution. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, elution with 1/1 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(3-hydroxy-3-methyl-but-1-ynyl)-pyrazin-2-yl]-propionamide (412 mg, 84%) as a fluffy solid: (ES)+-HRMS m/e calcd for C24H28ClN3O4S (M+H)+ 490.1562, found 490.1553.

후처리

  1. customan oily black precipitate was obtained
  2. customThe top clear solution was decanted
  3. washthe oily precipitate was rinsed first with toluene (5 mL)
  4. dissolutionThe residue was dissolved in methylene chloride
  5. extractionextracted with methylene chloride
  6. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. washFlash chromatography (Merck Silica gel 60, 230–400 mesh, elution with 1/1 ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-3eba0c06980042fbad574c8695fa58b6
출처 데이터셋
uspto-grants-2006_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07132425B2

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