Triethylamine → Tricyclo[3.3.1.13,7]dec-2-yl (+/-)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-pyrazinyl)ethyl]-amino]ethyl]carbamate

HRID 54857Notes

Reaction equation

HRID 54857 reaction equation
[CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[O:11][C:12]([NH:14][C:15]([CH3:29])([C:26](O)=[O:27])[CH2:16][C:17]1[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[NH:19][CH:18]=1)=[O:13])[CH2:8]2.O.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.C(N(CC)CC)C.Cl.[N:64]1[CH:69]=[CH:68][N:67]=[CH:66][C:65]=1[CH2:70][CH2:71][NH2:72]>C(OCC)(=O)C.O>[NH:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:17]([CH2:16][C:15]([NH:14][C:12](=[O:13])[O:11][CH:2]2[CH:1]3[CH2:10][CH:5]4[CH2:6][CH:7]([CH2:9][CH:3]2[CH2:4]4)[CH2:8]3)([CH3:29])[C:26](=[O:27])[NH:72][CH2:71][CH2:70][C:65]2[CH:66]=[N:67][CH:68]=[CH:69][N:64]=2)=[CH:18]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 148025032-adamantyloxycarbonyl-alpha-methyl-DL-tryptophanHCID 190477972-Pyrazin-2-yl-ethylamine hydrochloride

Product 1

HCID 86747500Tricyclo[3.3.1.13,7]dec-2-yl (+/-)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-pyrazinyl)ethyl]-amino]ethyl]carbamateYield 63.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A room temperature solution of 0.40 g (1.01 mmol) of 2-adamantyloxycarbonyl-α-methyl-DL-tryptophan and 0.15 g (1.11 mmol) of 1-hydroxybenzotriazole hydrate in 15 mL of anhydrous ethyl acetate under N2 atmosphere was treated with 0.23 g (1.11 mmol) of 1,3-dicyclohexylcarbodiimide in one portion. The reaction was stirred for 1.75 hours and treated with 0.12 g (1.22 mmol) of triethylamine and 0.17 g (1.07 mmol) of 2-pyrazineethaneamine hydrochloride. The reaction as stirred for 1.75 hours and filtered. The filtrate was washed with aqueous 1M citric acid (2×15 mL), saturated aqueous NaHCO3 (2×15 mL), and saturated aqueous NaCl (15 mL), dried over Na2SO4, and concentrated in vacuo. The residue was treated with 1,2-dimethoxyethane (5 mL), allowed to stand at 0°-5° C. for 16 hours, filtered, and concentrated in vacuo. Chromatography (flash, SiO2, 230-400 mesh, 0.5% triethylamine/10% isopropanol/ethyl acetate eluant, 15×2.5 cm) gave a clear oil upon solvent removal. The residue was dissolved in methanol (10 mL) and water (1 mL) and concentrated in vacuo until a solid formed. The solid was suspended in water, filtered, and dried to give 0.32 g (63%) of the desired product as a white solid; mp 97°-101° C.; 1H NMR (CDCl3) δ1.4-2.0 (17H, m), 2.87 (2H, m), 3.29 (1H, d, J 15 Hz), 3.46 (1H, d, J 15 Hz), 3.62 (2H, m), 4.74 (1H, br s), 5.23 (1H, br s), 6.95 (2H, br s), 7.0-7.2 (2H, m), 7.33 (1H, d, J 8 Hz), 7.58 (1H, d, J 8 Hz), 8.20 (1H, br s), 8.37 (2H, s), 8.38 (1H, s).

Workup

  1. customThe reaction
  2. stirringas stirred for 1.75 hours
  3. filtrationfiltered
  4. washThe filtrate was washed with aqueous 1M citric acid (2×15 mL), saturated aqueous NaHCO3 (2×15 mL), and saturated aqueous NaCl (15 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. additionThe residue was treated with 1,2-dimethoxyethane (5 mL)
  8. waitto stand at 0°-5° C. for 16 hours
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customChromatography (flash, SiO2, 230-400 mesh, 0.5% triethylamine/10% isopropanol/ethyl acetate eluant, 15×2.5 cm) gave a clear oil
  12. customupon solvent removal
  13. dissolutionThe residue was dissolved in methanol (10 mL)
  14. concentrationwater (1 mL) and concentrated in vacuo until a solid
  15. customformed
  16. filtrationfiltered
  17. customdried

Sources & evidence

ORD record
ord-6529f8341a3d4b88b3a4ed5142daa9e7
Source dataset
uspto-grants-1997_04
Patent number
US05622983

Reaction notes

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