1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 53638145, compound

HRID 849881Notes

Reaction equation

HRID 849881 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[CH3:38][NH:39][C@H:40]([CH2:59][C:60]1[CH:69]=[CH:68][C:67]2[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=2)[CH:61]=1)[C:41]([NH:43][C@@H:44]([C:56](=[S:58])[NH2:57])[CH2:45][C:46]1[CH:55]=[CH:54][C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[CH:47]=1)=[O:42].C(N(C(C)C)CC)(C)C>C(Cl)Cl.C(OC)(C)(C)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14](=[O:16])[N:39]([CH3:38])[C@@H:40]([C:41](=[O:42])[NH:43][C@@H:44]([C:56](=[S:58])[NH2:57])[CH2:45][C:46]2[CH:55]=[CH:54][C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[CH:47]=2)[CH2:59][C:60]2[CH:69]=[CH:68][C:67]3[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=3)[CH:61]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 54555847HCID 54555847, compound

Product 1

HCID 53638145HCID 53638145, compoundYield 75.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 15413tert-Butyl methyl etherSolvent

Procedure

N-tert-Butyloxycarbonylpiperidin-4-carboxylic acid (97 mg; 0.424 mmol) was dissolved in methylene chloride (2 ml). HOAt (58 mg; 0.424 mmol) and EDAC (85 mg; 0.444 mmol) were added. The reaction mixture was stirred 15 min at RT. (2R)-2-Methylamino-3-(2-naphthyl)-N-((1R)-2-(2-naphthyl)-1-thiocarbamoylethyl)propionamide (17 mg; 0.386 mmol) was dissolved in methylene chloride (2 ml) and added. Diisopropylethylamine (0.073 ml; 0.424 mmol) was added and the reaction mixture was stirred 12 hours at room temperature. Tert-butylmethylether (25 ml) was added and the reaction mixture was washed with water (25 ml), aqueous sodium hydrogencarbonate (15 ml), aqueous sodiumhydrogensulfate (10%; 15 ml), water (15 ml) and dried (magnesium sulfate). The solvent was removed in vacuo and the residue was chromatographed on silica (3.5×30 cm) using gradient elution, starting with ethyl acetate/heptane (1:1) increasing to ethyl acetate/heptane (2:1) to afford 0.190 g of 4-(N-methyl-N-((1R)-2-(2-naphtyl)-1-((1R)-2-(2-naphthyl)-1-thiocarbamoylethylcarbamoyl)ethyl)carbamoyl)piperidine-1-carboxylic acid tert-butylester.

Workup

  1. additionadded
  2. stirringthe reaction mixture was stirred 12 hours at room temperature
  3. washthe reaction mixture was washed with water (25 ml), aqueous sodium hydrogencarbonate (15 ml), aqueous sodiumhydrogensulfate (10%; 15 ml), water (15 ml)
  4. dry with materialdried (magnesium sulfate)
  5. customThe solvent was removed in vacuo
  6. customthe residue was chromatographed on silica (3.5×30 cm)
  7. washelution
  8. temperatureincreasing to ethyl acetate/heptane (2:1)

Sources & evidence

ORD record
ord-884136114c21443a859b83c3778295cf
Source dataset
uspto-grants-2000_01
Patent number
US06013658

Reaction notes

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