1-Hydroxybenzotriazole → Tert-butyl{trans-2-[4-({[3-(2-oxopiperidin-1-yl)phenyl]carbonyl}amino)phenyl]cyclopropyl}-carbamate

HRID 922518Notes

Reaction equation

HRID 922518 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[CH2:10][C@H:9]2[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[CH:4][CH:3]=1.[O:19]=[C:20]1[CH2:25][CH2:24][CH2:23][CH2:22][N:21]1[C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=1)[C:29](O)=[O:30].Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1>C(#N)C.O.C(N(CC)CC)C>[C:14]([O:13][C:12](=[O:18])[NH:11][C@@H:9]1[CH2:10][C@H:8]1[C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:29]([C:28]2[CH:32]=[CH:33][CH:34]=[C:26]([N:21]3[CH2:22][CH2:23][CH2:24][CH2:25][C:20]3=[O:19])[CH:27]=2)=[O:30])=[CH:3][CH:4]=1)([CH3:15])([CH3:17])[CH3:16]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 246890393-(2-Oxopiperidin-1-yl)benzoic acidHCID 86673140rac-tert-butyl N-[(1R,2S)-2-(4-aminophenyl)cyclopropyl]carbamate

Product 1

HCID 131734969Tert-butyl{trans-2-[4-({[3-(2-oxopiperidin-1-yl)phenyl]carbonyl}amino)phenyl]cyclopropyl}-carbamateYield 15.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of tert-butyl [trans-2-(4-aminophenyl)cyclopropyl]carbamate (230 mg) described in a document (J. Am. Chem. Soc., 2010, 132, 6827.) in acetonitrile (7 mL) were added 3-(2-oxopiperidin-1-yl)benzoic acid (169 mg), N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (177 mg), 1-hydroxybenzotriazole (125 mg) and triethylamine (128 μL). The mixture was stirred at room temperature overnight and water was added. The mixture was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (53.4 mg).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washthe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-c1a4212c7c2f4f5e9e341fa4b986725f
Source dataset
uspto-grants-2016_03
Patent number
US09278931B2

Reaction notes

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