Sodium Iodide → HCID 20740255, compound

HRID 1883157Notes

Reaction equation

HRID 1883157 reaction equation
[C:1]([CH2:3][NH:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][CH2:9][C@@H:8]1[NH:13][C:14]([C:16]1[N:17]([CH2:26][CH2:27][CH2:28]O)[C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[C:20]([Cl:25])[CH:19]=2)=[O:15])=[O:6])#[N:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[CH3:57][S:58]([O-:60])=[O:59].[Na+].[I-].[Na+]>CN(C=O)C>[C:1]([CH2:3][NH:4][C:5]([C@@H:7]1[CH2:12][CH2:11][CH2:10][CH2:9][C@@H:8]1[NH:13][C:14]([C:16]1[N:17]([CH2:26][CH2:27][CH2:28][S:58]([CH3:57])(=[O:60])=[O:59])[C:18]2[C:23]([CH:24]=1)=[CH:22][CH:21]=[C:20]([Cl:25])[CH:19]=2)=[O:15])=[O:6])#[N:2]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 2733271Sodium methanesulfinateHCID 60083697HCID 60083697, compound

Product 1

HCID 20740255HCID 20740255, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 150 mg (0.36 mmol) of 6-Chloro-1-(3-hydroxy-propyl)-1H-indole-2-carboxylic acid [(1S,2R)-2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide (from Example 45) dissolved in 5 mL DMF was added 151 mg (0.58 mmol) triphenylphosphine. At 0° C., N-bromosuccinimide (104 mg, 0.58 mmol) was added in portions. After stirring at room temperature for 30 minutes, sodium methane sulfinate (88 mg, 0.73 mmol) and sodium iodide (6 mg, 0.036 mmol) were added in portions. The reaction mixture was then stirred at 70° C. for 3 hours, cooled to room temperature, partitioned between ethyl acetate and 5% aqueous sodium thiosulfate solution, washed with water, dried over magnesium sulfate, and concentrated. Column chromatography, eluting with 70% ethyl acetate in hexane, followed by recrystallization from ether provided 50 mg of 6-chloro-1-(3-methanesulfonyl-propyl)-1H-indole-2-carboxylic acid [(1S,2R)-2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide. HPLC: 87% pure, yield: 30%, MS: 479 (M H+).

Workup

  1. stirringThe reaction mixture was then stirred at 70° C. for 3 hours
  2. temperaturecooled to room temperature
  3. custompartitioned between ethyl acetate and 5% aqueous sodium thiosulfate solution
  4. washwashed with water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. washColumn chromatography, eluting with 70% ethyl acetate in hexane
  8. customfollowed by recrystallization from ether

Sources & evidence

ORD record
ord-b4237a4f317b4ed08103bd99d7a5747e
Source dataset
uspto-grants-2004_07
Patent number
US06759428B2

Reaction notes

Loading…