2,6-Lutidine → HCID 10075193, compound

HRID 854840Notes

Reaction equation

HRID 854840 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:22][CH2:21][C:20](=[O:23])[CH2:19][CH2:18]2)[C:13](O)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[NH2:51][C:52]1[CH:57]=[N:56][C:55]([Br:58])=[CH:54][N:53]=1.N1C(C)=CC=CC=1C>C(Cl)Cl>[Br:58][C:55]1[N:56]=[CH:57][C:52]([NH:51][C:13](=[O:14])[C@@H:12]([C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=2)[CH2:16][CH:17]2[CH2:18][CH2:19][C:20](=[O:23])[CH2:21][CH2:22]2)=[N:53][CH:54]=1

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimide2×HCID 5995392-Amino-5-bromopyrazineHCID 210518482(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionic acid

Product 1

HCID 10075193HCID 10075193, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionic acid (200 mg, 0.56 mmol) and triphenylphosphine (195 mg, 0.73 mmol) in methylene chloride (4.0 mL) cooled to 0° C. was treated with N-bromosuccinimide (128 mg, 0.73 mmol) in small portions. After the complete addition of N-bromosuccinimide, the reaction mixture was allowed to warm to 25° C. over 30 min. The bright orange reaction mixture was then treated with 2-amino-5-bromopyrazine (200 mg, 1.12 mmol, prepared according to Tetrahedron 1988, 44, 2977-2983) and 2,6-lutidine (0.28 mL, 2.24 mmol). The resulting reaction mixture was stirred at 25° C. for 4 h. The reaction mixture was then diluted with methylene chloride (25 mL) and was successively washed with a 10% aqueous hydrochloric acid solution 1×20 mL), a saturated aqueous sodium bicarbonate solution 1×20 mL) and water 1×20 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 65/35 hexanes/ethyl acetate eluted to 4/6 hexanes/ethyl acetate) afforded N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionamide (120 mg, 42%) as an off-white foam: [α]23589=−24.6° (c=0.50, chloroform); EI-HRMS m/e calcd for C20H21BrClN3O4S (M+Na)+ 536.0017. found 536.0022.

Workup

  1. customThe resulting reaction mixture
  2. washwas successively washed with a 10% aqueous hydrochloric acid solution 1×20 mL), a saturated aqueous sodium bicarbonate solution 1×20 mL) and water 1×20 mL),
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. washBiotage chromatography (FLASH 40S, Silica, 65/35 hexanes/ethyl acetate eluted to 4/6 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-c4ed4136d8614ed18ba4ff224aff58b3
Source dataset
uspto-grants-2007_08
Patent number
US07259166B2

Reaction notes

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