Hydrochloric Acid → 6-Chloro-1h-indole-2-carboxylic acid[2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide

HRID 1883128Notes

Reaction equation

HRID 1883128 reaction equation
[C:1]([CH2:3][NH:4][C:5]([CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]1[NH2:13])=[O:6])#[N:2].C1C=CC2N(O)N=NC=2C=1.[Cl:24][C:25]1[CH:33]=[C:32]2[C:28]([CH:29]=[C:30]([C:34](O)=[O:35])[NH:31]2)=[CH:27][CH:26]=1.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C>[C:1]([CH2:3][NH:4][C:5]([CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]1[NH:13][C:34]([C:30]1[NH:31][C:32]2[C:28]([CH:29]=1)=[CH:27][CH:26]=[C:25]([Cl:24])[CH:33]=2)=[O:35])=[O:6])#[N:2]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 855846-Chloro-1H-indole-2-carboxylic acidHCID 20740295HCID 20740295, compound

Product 1

HCID 235102346-Chloro-1h-indole-2-carboxylic acid[2-(cyanomethyl-carbamoyl)-cyclohexyl]-amideYield 49.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-amino-cyclohexanecarboxylic acid cyanomethyl-amide (6.4 g, 35.31 mmol) in DMF (70 ml), were added HOBT (5.25 g, 38.84 mmol), 6-chloro-2-indolecarboxylic acid (7.60 g, 38.84 mmol), N-methylmorpholine (19.4 ml, 176.45 mmol), and EDCI (7.45 g, 38.84 mmol) respectively at 0° C. The reaction was stirred at room temperature for 16 hours, then 1N HCl (500 ml) was added and the resulting cloudy solution was extracted with ethyl acetate (3×200 ml). The organic layer was filtered through a Celite pad, washed with 1N NaOH (200 ml), brine (200 ml), dried over magnesium sulfate and concentrated in vacuo yielding 6-chloro-1H-indole-2-carboxylic acid [2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide, (6.25 g, 49%).

Workup

  1. extractionthe resulting cloudy solution was extracted with ethyl acetate (3×200 ml)
  2. filtrationThe organic layer was filtered through a Celite pad
  3. washwashed with 1N NaOH (200 ml), brine (200 ml)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-311a4fed954b48399c2269b89e949a57
Source dataset
uspto-grants-2004_07
Patent number
US06759428B2

Reaction notes

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