1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (1R*,2R*)-4-benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine

HRID 546510Notes

Reaction equation

HRID 546510 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]1[CH2:14][C@@H:13]([NH:15][C:16]([C:18]2[NH:19][C:20]3[C:25]([CH:26]=2)=[CH:24][C:23]([Cl:27])=[CH:22][CH:21]=3)=[O:17])[C@H:12]([NH2:28])[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][N:30]1[CH2:35][CH2:34][C:33]2[N:36]=[C:37]([C:39]([O-])=[O:40])[S:38][C:32]=2[CH2:31]1.[Li+].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O>[CH2:1]([O:8][CH2:9][CH:10]1[CH2:14][C@@H:13]([NH:15][C:16]([C:18]2[NH:19][C:20]3[C:25]([CH:26]=2)=[CH:24][C:23]([Cl:27])=[CH:22][CH:21]=3)=[O:17])[C@H:12]([NH:28][C:39]([C:37]2[S:38][C:32]3[CH2:31][N:30]([CH3:29])[CH2:35][CH2:34][C:33]=3[N:36]=2)=[O:40])[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 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 58822261(1R*,2R*)-4-Benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-1,2-cyclopentanediamine

Product 1

HCID 68905458(1R*,2R*)-4-benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamineYield 30.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(1R*,2R*)-4-Benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-1,2-cyclopentanediamine (794 mg) was dissolved in N,N-dimethylformamide (150 ml), and lithium 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (694 mg), 1-hydroxybenzotriazole monohydrate (61 mg) and 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (1.15 g) were added to stir the mixture overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and water was added to the residue to conduct extraction with dichloromethane. The resultant organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by preparative thin-layer chromatography (dichloromethane:acetone=2:1) to obtain Stereoisomer A (378 mg) and Stereoisomer B (354 mg) of (1R*,2R*)-4-benzyloxymethyl-N1-[(5-chloroindol-2-yl)carbonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclopentanediamine.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and water
  2. additionwas added to the residue
  3. extractionextraction with dichloromethane
  4. dry with materialThe resultant organic layer was dried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customthe residue was purified by preparative thin-layer chromatography (dichloromethane:acetone=2:1)

Sources & evidence

ORD record
ord-e0e464dcb849476a89d978815d9f15e4
Source dataset
uspto-grants-2011_05
Patent number
US07935824B2

Reaction notes

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