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

HRID 54858Notes

Reaction equation

HRID 54858 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]([OH:28])=O)[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.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.Cl.[O:61]1[CH:65]=[CH:64][CH:63]=[C:62]1[CH2:66][CH2:67][NH2:68]>CN(C)C=O.C(OCC)C.O>[O:61]1[CH:65]=[CH:64][CH:63]=[C:62]1[CH2:66][CH2:67][NH:68][C:26](=[O:28])[C:15]([NH:14][C:12](=[O:13])[O:11][CH:2]1[CH:3]2[CH2:4][CH:5]3[CH2:6][CH:7]([CH2:8][CH:1]1[CH2:10]3)[CH2:9]2)([CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][CH:18]=1)[CH3:29]

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 130455482-(Furan-2-yl)ethan-1-amine hydrochlorideHCID 148025032-adamantyloxycarbonyl-alpha-methyl-DL-tryptophan

Product 1

HCID 86747501Tricyclo [3.3.1.13,7]dec-2-yl (+/-)-[2-[[2-(2-furanyl)ethyl]amino]-1-(1H-indol-3-ylmethyl)-1-methyl-2-oxoethyl]carbamateYield 70%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

A room temperature solution of 0.30 g (0.76 mmol) of 2-adamantyloxycarbonyl-α-methyl-DL-tryptophan and 0.11 g (0.81 mmol) of 1-hydroxybenzotriazole hydrate in 10 mL of anhydrous N,N-dimethylformamide under N2 atmosphere was treated with 0.16 g (0.83 mmol 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in one portion. The reaction was stirred for 1.75 hours at room temperature and treated with 0.09 g (0.93 mmol) of triethylamine and 0.13 g (0.88 mmol) of 2-furanethaneamine hydrochloride. The reaction was stirred for 21 hours at room temperature, then partitioned between saturated aqueous NaHCO3 (50 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (20 mL). The combined organic extracts were washed with aqueous 1M citric acid (3×15 mL), water (2×15 mL), saturated aqueous NaHCO3 (15 mL), water (15 mL), and saturated aqueous NaCl (15 mL), dried over Na2SO4, and concentrated in vacuo. The residue was passed through a plug of SiO2 (70×230 mesh, 50% ethyl acetate-hexane eluant, 15 mL medium sintered glass funnel) to give a clear glass. The residue was dissolved in diethyl ether (3 mL), methanol (5 mL), and water (2 mL), and concentrated in vacuo until a solid formed. The mixture was treated with water, filtered, and dried to give 0.26 g (70%) of the desired product as a white solid, mp 87°-97° C.; 1H NMR (CDCl3) δ1.5-2.0 (17H, m), 2.67-2.74 (2H, m), 3.29 (1H, d, J 15 Hz), 3.46-3.49 (3H, m), 4.82 (1H, br s), 5.16 (1H, br s), 5.95 (1H, d, J 3 Hz), 6.25 (1H, dd, J 3 Hz and J 2 Hz), 6.37 (1H, br s), 6.97 (1H, d, J 2 Hz), 7.1-7.3 (3H, m), 7.36 (1H, d, J 8 Hz), 7.59 (1H, d, J 8 Hz), 8.18 (1H, br s).

Workup

  1. stirringThe reaction was stirred for 21 hours at room temperature
  2. custompartitioned between saturated aqueous NaHCO3 (50 mL) and ethyl acetate (50 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
  4. washThe combined organic extracts were washed with aqueous 1M citric acid (3×15 mL), water (2×15 mL), saturated aqueous NaHCO3 (15 mL), water (15 mL), and saturated aqueous NaCl (15 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto give a clear glass
  8. concentrationmethanol (5 mL), and water (2 mL), and concentrated in vacuo until a solid
  9. customformed
  10. filtrationfiltered
  11. customdried

Sources & evidence

ORD record
ord-890fcb229a5d48ab8c4fb7b17c66d694
Source dataset
uspto-grants-1997_04
Patent number
US05622983

Reaction notes

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