1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → tert-Butyl {2-[({5-[(tert-butoxycarbonyl)amino]-3-methylthiophen-2-yl}carbonyl)(methyl)amino]ethyl}methylcarbamate

HRID 446584Notes

Reaction equation

HRID 446584 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]([OH:16])=O)=[C:11]([CH3:17])[CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:18][N:19]([CH2:27][CH2:28][NH:29][CH3:30])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].Cl.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([NH:8][C:9]1[S:13][C:12]([C:14]([N:29]([CH3:30])[CH2:28][CH2:27][N:19]([CH3:18])[C:20](=[O:26])[O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:16])=[C:11]([CH3:17])[CH:10]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 14403871tert-Butyl methyl(2-(methylamino)ethyl)carbamateHCID 434168385-((tert-Butoxycarbonyl)amino)-3-methylthiophene-2-carboxylic acid

Product 1

HCID 86663470tert-Butyl {2-[({5-[(tert-butoxycarbonyl)amino]-3-methylthiophen-2-yl}carbonyl)(methyl)amino]ethyl}methylcarbamateYield 79%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

The compound (600 mg, 2.33 mmol) obtained in Example 89a and tert-butyl methyl[2-(methylamino)ethyl]carbamate (439 mg, 2.33 mmol) described in the literature (J. Med. Chem. 1990, 33, 97) were dissolved in methylene chloride (23 mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (670 mg, 3.50 mmol) and 4-dimethylaminopyridine (14 mg, 0.117 mmol) were added, and the mixture was stirred at room temperature for 1.5 hours. The solvent was evaporated under reduced pressure, 1 N hydrochloric acid was added to the resulting residue, the mixture was extracted with ethyl acetate, and then the organic layer was washed with saturated sodium chloride solution. The organic layer was dried with anhydrous sodium sulfate, then the solvent was evaporated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1, v/v) to give the title compound (757 mg; yield, 79%) as a light yellow solid.

Workup

  1. customThe solvent was evaporated under reduced pressure, 1 N hydrochloric acid
  2. additionwas added to the resulting residue
  3. extractionthe mixture was extracted with ethyl acetate
  4. washthe organic layer was washed with saturated sodium chloride solution
  5. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customthe resulting residue was purified by silica gel column chromatography (hexane

Sources & evidence

ORD record
ord-fb9c7a073fac4ace99bd3b15a581d7aa
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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