1-Bromo-3-chloropropane → HCID 20740305, compound

HRID 1883130Notes

Reaction equation

HRID 1883130 reaction equation
[C:1]([CH:3]([NH:8][C:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[NH:17][C:18]([C:20]1[NH:21][C:22]2[C:27]([CH:28]=1)=[CH:26][CH:25]=[C:24]([Cl:29])[CH:23]=2)=[O:19])=[O:10])[CH2:4][CH:5]([CH3:7])[CH3:6])#[N:2].[H-].[Na+].Br[CH2:33][CH2:34][CH2:35][Cl:36]>CN(C=O)C>[C:1]([CH:3]([NH:8][C:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[NH:17][C:18]([C:20]1[N:21]([CH2:33][CH2:34][CH2:35][Cl:36])[C:22]2[C:27]([CH:28]=1)=[CH:26][CH:25]=[C:24]([Cl:29])[CH:23]=2)=[O:19])=[O:10])[CH2:4][CH:5]([CH3:7])[CH3:6])#[N:2]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydrideHCID 20740311HCID 20740311, compound

Product 1

HCID 20740305HCID 20740305, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-chloro-1H-indole-2-carboxylic acid [2-(1-cyano-3-methyl-butylcarbamoyl)-cyclohexyl]-amide from Example 18 (0.428 g, 1.03 mmol) in DMF (3.5 ml) were added NaH (60% dispersion in mineral oil) (0.062 g, 1.54 mmol) at 0° C. The slurry was then stirred at room temperature for one hour followed by the addition of 1-bromo-3-chloropropane (0.13 ml, 1.34 mmol). Reaction was stirred overnight at room temperature and partitioned between 1 N HCl and ethyl acetate. The organic layer was washed with water, brine, dried over magnesium sulfate and concentrated in vacuo. The resulting oil was chromatographed on preparatory silica plates, eluting with 2.5% MeOH/dichloromethane, and yielding 6-chloro-1-(3-chloro-propyl)-1H-indole-2-carboxylic acid [2-(1-cyano-3-methyl-butylcarbamoyl)-cyclohexyl]-amide (0.323 g, 64%). [M+H=492].

Workup

  1. customReaction
  2. stirringwas stirred overnight at room temperature
  3. custompartitioned between 1 N HCl and ethyl acetate
  4. washThe organic layer was washed with water, brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe resulting oil was chromatographed on preparatory silica plates
  8. washeluting with 2.5% MeOH/dichloromethane

Sources & evidence

ORD record
ord-6cedab6d9f3a4b088c7b2ec81c9f4bb6
Source dataset
uspto-grants-2004_07
Patent number
US06759428B2

Reaction notes

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