Diisopropylethylamine → N-[(1R*,2S*)-2-Aminocyclopropyl]-5-chloroindole-2-carboxamide

HRID 902837Notes

Reaction equation

HRID 902837 reaction equation
O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C.Cl.[C@@H:34]1([NH2:38])[CH2:36][C@@H:35]1[NH2:37].[Cl:39][C:40]1[CH:41]=[C:42]2[C:46](=[CH:47][CH:48]=1)[NH:45][C:44]([C:49](O)=[O:50])=[CH:43]2>CN(C)C=O>[NH2:37][C@H:35]1[CH2:36][C@H:34]1[NH:38][C:49]([C:44]1[NH:45][C:46]2[C:42]([CH:43]=1)=[CH:41][C:40]([Cl:39])=[CH:48][CH:47]=2)=[O:50]

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 66785209cis-1,2-Cyclopropanediamine hydrochloride

Product 1

HCID 18442851N-[(1R*,2S*)-2-Aminocyclopropyl]-5-chloroindole-2-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Hydroxybenzotriazole monohydrate (377 mg), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (642 mg) and diisopropylethylamine (1.95 ml) were added to a solution of cis-1,2-cyclopropanediamine hydrochloride (J. Med. Chem., 1998, Vol. 41, pp. 4723-4732) (405 mg) and 5-chloroindole-2-carboxylic acid (546 mg) in N,N-dimethylformamide (10 ml) at room temperature, and the mixture was stirred for 50 hours. After the reaction mixture was concentrated under reduced pressure, methylene chloride (50 ml) and a saturated solution (200 ml) of sodium hydrogencarbonate were added to separate colorless solid deposited by filtration. The filtrate was extracted with methylene chloride. After the resultant organic layers were combined and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain residue. The residue was purified by flash column chromatography on silica gel (methylene chloride:methanol=100:7→10:1) to obtain the title compound (110 mg).

Workup

  1. concentrationAfter the reaction mixture was concentrated under reduced pressure, methylene chloride (50 ml)
  2. additiona saturated solution (200 ml) of sodium hydrogencarbonate were added
  3. customto separate colorless solid
  4. filtrationdeposited by filtration
  5. extractionThe filtrate was extracted with methylene chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customto obtain residue
  9. customThe residue was purified by flash column chromatography on silica gel (methylene chloride:methanol=100:7→10:1)

Sources & evidence

ORD record
ord-db882049ef5a4426806c66f36c94383d
Source dataset
uspto-grants-2008_04
Patent number
US07365205B2

Reaction notes

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