1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (+/-)-cis-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopropanediamine hydrochloride

HRID 459551Notes

Reaction equation

HRID 459551 reaction equation
O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[Cl:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29]([C:34]([NH:36][C@@H:37]1[CH2:39][C@@H:38]1[NH2:40])=[O:35])=[CH:28]2.[CH3:41][N:42]1[CH2:47][CH2:46][C:45]2[N:48]=[C:49]([C:51]([O-])=[O:52])[S:50][C:44]=2[CH2:43]1.[Li+]>CN(C)C=O>[ClH:24].[Cl:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29]([C:34]([NH:36][C@@H:37]1[CH2:39][C@@H:38]1[NH:40][C:51]([C:49]1[S:50][C:44]3[CH2:43][N:42]([CH3:41])[CH2:47][CH2:46][C:45]=3[N:48]=1)=[O:52])=[O:35])=[CH:28]2

Participants

6

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 18442851N-[(1R*,2S*)-2-Aminocyclopropyl]-5-chloroindole-2-carboxamideHCID 23704331Lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate

Product 1

HCID 68907574(+/-)-cis-N1-[(5-Chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopropanediamine hydrochlorideYield 71.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Hydroxybenzotriazole monohydrate (71 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (100 mg) were added to a solution with (±)-cis-N-[(5-chloroindol-2-yl)carbonyl]-1,2-cyclopropanediamine (108 mg) and lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (124 mg) dissolved in N,N-dimethylformamide (3 ml) at room temperature, and the mixture was stirred for 8 days. After concentrating the reaction mixture under reduced pressure using a vacuum pump, water (50 ml) and a saturated aqueous solution (50 ml) of sodium hydrogencarbonate were added to the residue to conduct extraction with dichloromethane. The resultant organic layers were collected and dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by preparative thin-layer chromatography on silica gel (dichloromethane:methanol=10:1). After 1N hydrochloric acid, dichloromethane and methanol were added to the thus-obtained amorphous substance, the mixture was concentrated to obtain the title compound (72 mg) as a colorless solid.

Workup

  1. concentrationAfter concentrating the reaction mixture under reduced pressure
  2. additiona saturated aqueous solution (50 ml) of sodium hydrogencarbonate were added to the residue
  3. extractionextraction with dichloromethane
  4. customThe resultant organic layers were collected
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customthe residue was purified by preparative thin-layer chromatography on silica gel (dichloromethane:methanol=10:1)
  8. additionAfter 1N hydrochloric acid, dichloromethane and methanol were added to the thus-obtained amorphous substance
  9. concentrationthe mixture was concentrated

Sources & evidence

ORD record
ord-b2fd3a4f76b64bf7964f13d54bc1aba2
Source dataset
uspto-grants-2007_03
Patent number
US07192968B2

Reaction notes

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