Hydrochloric Acid → (1R*,2R*)-N1-[(5-Chloroindol-2-yl)carbonyl]-4-methoxycarbonyl-N2-[(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine hydrochloride

HRID 546508Notes

Reaction equation

HRID 546508 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@@H:14]1[CH2:18][CH:17]([C:19]([O:21][CH3:22])=[O:20])[CH2:16][C@H:15]1[NH2:23])=[O:12])=[CH:5]2.[CH3:24][N:25]1[CH2:30][CH2:29][C:28]2[N:31]=[C:32]([C:34]([O-])=[O:35])[S:33][C:27]=2[CH2:26]1.[Li+].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.Cl>CN(C)C=O.CO.C(O)C>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([NH:13][C@@H:14]1[CH2:18][CH:17]([C:19]([O:21][CH3:22])=[O:20])[CH2:16][C@H:15]1[NH:23][C:34]([C:32]1[S:33][C:27]3[CH2:26][N:25]([CH3:24])[CH2:30][CH2:29][C:28]=3[N:31]=1)=[O:35])=[O:12])=[CH:5]2

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 23704331Lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylateHCID 58822247(1R*,2R*)-N1-[(5-Chloroindol-2-yl)carbonyl]-4-methoxycarbonyl-1,2-cyclopentanediamine

Product 1

HCID 68905632(1R*,2R*)-N1-[(5-Chloroindol-2-yl)carbonyl]-4-methoxycarbonyl-N2-[(5-methyl-4,5,6,7-tetrahydro-thiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine hydrochloride

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

(1R*,2R*)-N1-[(5-Chloroindol-2-yl)carbonyl]-4-methoxycarbonyl-1,2-cyclopentanediamine (mixture of stereoisomers) (3.42 g) was dissolved in N,N-dimethylformamide (20 ml), and lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (3.12 g), 1-hydroxybenzotriazole monohydrate (689 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.89 g) were added to stir the mixture overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and a saturated aqueous solution of sodium hydrogencarbonate and dichloromethane were added to the residue to conduct liquid separation. The resultant water layer was extracted 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 flash column chromatography on silica gel (dichloromethane:methanol=97:3→19:1) to obtain Stereoisomer A (585 mg) and Stereoisomer B (1.31 g). Each stereoisomer was dissolved in methanol, and a 1N ethanol solution of hydrochloric acid was added thereto. After the solvent was distilled off under reduced pressure, ethyl acetate was added to the residue. Precipitate formed was collected by filtration to obtain the title compounds [Stereoisomer A (573 mg) and Stereoisomer B (1.26 g)] as pale yellow solids.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additiona saturated aqueous solution of sodium hydrogencarbonate and dichloromethane were added to the residue
  3. customliquid separation
  4. extractionThe resultant water layer was extracted with dichloromethane
  5. customThe resultant organic layers were collected
  6. dry with materialdried over anhydrous sodium sulfate
  7. distillationThe solvent was distilled off under reduced pressure
  8. customthe residue was purified by flash column chromatography on silica gel (dichloromethane:methanol=97:3→19:1)
  9. customto obtain Stereoisomer A (585 mg) and Stereoisomer B (1.31 g)
  10. distillationAfter the solvent was distilled off under reduced pressure, ethyl acetate
  11. additionwas added to the residue
  12. customPrecipitate formed
  13. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-d41f99d1068d419d8bffa19042bb415d
Source dataset
uspto-grants-2011_05
Patent number
US07935824B2

Reaction notes

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