2,6-Lutidine → HCID 10412416, compound

HRID 2214131Notes

Reaction equation

HRID 2214131 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]([Cl:58])=[CH:54][N:53]=1.N1C(C)=CC=CC=1C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:12]([CH2:16][CH:17]2[CH2:18][CH2:19][C:20](=[O:23])[CH2:21][CH2:22]2)[C:13]([NH:51][C:52]2[CH:57]=[N:56][C:55]([Cl:58])=[CH:54][N:53]=2)=[O:14])[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:9])=[O:10]

Participants

7

Reactant 5

HCID 79372,6-LutidineHCID 11776TriphenylphosphineHCID 67184N-bromobutanimide2×HCID 128084192-Amino-5-chloropyrazineHCID 210518482(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-propionic acid

Product 1

HCID 10412416HCID 10412416, compoundYield 52%

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 (prepared as in Example 60, 200 mg, 0.56 mmol) and triphenylphosphine (192 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-chloropyrazine (145 mg, 1.12 mmol) 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, 13/7 hexanes/ethyl acetate to 2/3 hexanes/ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-N-(5-chloro-pyrazin-2-yl)-3-(4-oxo-cyclohexyl)-propionamide (137 mg, 52%) as a light yellow foam: [α]23589=−27.35° (c=0.49, chloroform); EI-HRMS m/e calcd for C20H21Cl2N3O4S (M+H)+ 470.0703, found 470.0705.

Workup

  1. customThe resulting reaction mixture
  2. washwas successively washed with a 10% aqueous hydrochloric acid solution (1×20 mL)
  3. dry with materiala saturated aqueous sodium bicarbonate solution (1×20 mL) and water (1×20 mL), dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c86cb7e9c84a4e169c49f058d082d65d
Source dataset
uspto-grants-2006_09
Patent number
US07105671B2

Reaction notes

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