Triethylamine → N-[1(R)-[spiro[1H-indene-1,4'-piperidin]-1'-yl-carbonyl]-2-(1H-indol-3-yl)ethyl]carbamic benzyl ester

HRID 1902151Notes

Reaction equation

HRID 1902151 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([C:23](O)=[O:24])[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH:27]1[CH2:32][CH2:31][C:30]2([C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:34]=[CH:33]2)[CH2:29][CH2:28]1.C(N(CC)CC)C.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC>C(Cl)(Cl)Cl.C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:10])[NH:11][C@@H:12]([C:23]([N:27]1[CH2:32][CH2:31][C:30]2([C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH:34]=[CH:33]2)[CH2:29][CH2:28]1)=[O:24])[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 700663N-(Benzyloxycarbonyl)-D-tryptophanHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22509344Spiro[indene-1,4'-piperidine] hydrochloride

Product 1

HCID 22867454N-[1(R)-[spiro[1H-indene-1,4'-piperidin]-1'-yl-carbonyl]-2-(1H-indol-3-yl)ethyl]carbamic benzyl esterYield 79.5%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-benzyloxycarbonyl-(D)-tryptophan (1.69 g, 5.0 mmole) in 70 mL of chloroform at room temperature was added spiro[1H-indene-1,4'-piperidine]hydrochloride (J. Med. Chem. 1992, 35, 2033)(1.21 g, 5.5 mmole), triethylamine (0.73 mL, 5.25 mmole) followed by 1-hydroxybenzotriazole hydrate (0.74 g, 5.5 mmole) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.05 g, 5.5 mmole). After 12 hours at room temperature, the mixture was diluted with methylene chloride and then washed sequentially with water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatatron (hexanes/ethyl acetate=1/1) to give 2.01 g (79%) of the title compound.

Workup

  1. washwashed sequentially with water and brine
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified by chromatatron (hexanes/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-8c7acc649ba44eb28458d5575624900d
Source dataset
uspto-grants-1996_11
Patent number
US05578593

Reaction notes

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