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

HRID 54853

Reaction equation

HRID 54853 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.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC.C(N(CC)CC)C.Cl.[S:59]1[CH:63]=[CH:62][CH:61]=[C:60]1[CH2:64][CH2:65][NH2:66]>C(OCC)(=O)C.CN(C)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:66][CH2:65][CH2:64][C:60]2[S:59][CH:63]=[CH:62][CH:61]=2)=[CH:18]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 4585722-Thiopheneethylamine, hydrochlorideHCID 148025032-adamantyloxycarbonyl-alpha-methyl-DL-tryptophan

Product 1

HCID 86747496Tricyclo [3.3.1.13,7]dec-2-yl (+/-)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-thienyl)ethyl]amino]ethyl]carbamateYield 61%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a solution of 2-adamantyloxycarbonyl-α-methyl-DL-tryptophan (0.401 g, 1.01 mmol) in dry ethyl acetate (6 mL) and N,N-dimethylformamide (4 mL) under nitrogen atmosphere was added 1-hydroxybenzotriazole (0.138 g, 1.02 mmol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.199 g, 1.04 mmol). this mixture was stirred 2 hours, then triethylamine (0.18 mL, 1.3 mmol) and 2-thiopheneethaneamine hydrochloride (0.214 g, 1.30 mmol) were added. After stirring the resulting mixture an additional 18 hours, the mixture was diluted with ethyl acetate (20 mL), and washed with aqueous 1N citric acid, saturated aqueous sodium bicarbonate, and brine solutions. The organic phase was dried over MgSO4, concentrated, purified by flash chromatography (SiO2, 4×20 cm, 230-400 mesh, 67% ethyl acetate/hexane eluant), and dried for 48 hours under vacuum at 60° C. to provide 0.310 g (61%) of product; 1H NMR (CDCl3) δ1.49-1.60 (2H, m), 1.55 (3H, s), 1.65-2.00 (12H, m), 2.88 (2H, t, J 6 Hz), 3.26 (1H, d, J 14 Hz), 3.40-3.60 (3H, m), 4.82 (1H, br s), 5.17 (1H, br s), 6.36 (1H, br s), 6.69 (1H, d, J 2 Hz), 6.85-6.90 (1H, m), 6.95 (1H, d, J 2 Hz), 7.00-7.22 (3H, m), 7.36 (1H, d, J 8 Hz), 7.58 (1H, d, J 8 Hz), 8.29 (1H, br s).

Workup

  1. stirringAfter stirring the resulting mixture an additional 18 hours
  2. washwashed with aqueous 1N citric acid, saturated aqueous sodium bicarbonate, and brine solutions
  3. dry with materialThe organic phase was dried over MgSO4
  4. concentrationconcentrated
  5. custompurified by flash chromatography (SiO2, 4×20 cm, 230-400 mesh, 67% ethyl acetate/hexane eluant)
  6. customdried for 48 hours under vacuum at 60° C.

Sources & evidence

ORD record
ord-aae5d8f5e363413680122ae21473a0ee
Source dataset
uspto-grants-1997_04
Patent number
US05622983

Linked notes

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