Triphenylphosphine → HCID 59086448, compound

HRID 398660Notes

Reaction equation

HRID 398660 reaction equation
[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[NH2:46][C:47]1[CH:52]=[N:51][CH:50]=[CH:49][N:48]=1>C(Cl)Cl>[CH:1]1([CH2:6][C@H:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17][CH3:18])=[CH:13][CH:12]=2)[C:8]([NH:46][C:47]2[CH:52]=[N:51][CH:50]=[CH:49][N:48]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimide2×HCID 78747AminopyrazineHCID 12069492HCID 12069492, compound

Product 1

HCID 59086448HCID 59086448, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2(R)-(4-methylsulfanyl-phenyl)-propionic acid (529 mg, 2.0 mmol) and triphenylphosphine (892 mg, 3.4 mmol) in methylene chloride (10 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (605 mg, 3.4 mmol) in small portions. The reaction mixture color changed from light yellow to a darker yellow then to brown. After the complete addition of the N-bromosuccinimide, the reaction mixture was allowed to warm to 25° C. over 30 min. The brown reaction mixture was then treated with 2-aminopyrazine (476 mg, 5.0 mmol). The resulting reaction mixture was stirred at 25° C. for 19 h. The reaction mixture was then concentrated in vacuo to remove methylene chloride. The remaining black residue was diluted with a 10% aqueous hydrochloric acid solution (40 mL) and then extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 65/35 hexanes/ethyl acetate) afforded 3-cyclopentyl-2(R)-(4-methylsulfanyl-phenyl)-N-pyrazin-2-yl-propionamide (102 mg, 15%) as a white solid: mp 128-130° C., [α]23589=−103.1° (c=0.032, chloroform); EI-HRMS m/e calcd for C19H23N3OS (M+) 341.1562, found 341.1563.

Workup

  1. customThe resulting reaction mixture
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. customto remove methylene chloride
  4. additionThe remaining black residue was diluted with a 10% aqueous hydrochloric acid solution (40 mL)
  5. extractionextracted with ethyl acetate (3×25 mL)
  6. washThe combined organic layers were washed with a saturated aqueous sodium chloride solution (1×20 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a942124d81a64ae181f077df36e1a810
Source dataset
uspto-grants-2003_08
Patent number
US06610846B1

Reaction notes

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