1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-[1-(4-fluorophenyl)cyclobutyl]-2-(2-oxo-3-phenylpiperidin-1-yl)acetamide

HRID 1667183Notes

Reaction equation

HRID 1667183 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([NH2:13])[CH2:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.[O:14]=[C:15]1[CH:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:19][CH2:18][CH2:17][N:16]1[CH2:27][C:28](O)=[O:29].C(N=C=NCCCN(C)C)C>ClCCl>[F:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2([NH:13][C:28](=[O:29])[CH2:27][N:16]3[CH2:17][CH2:18][CH2:19][CH:20]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:15]3=[O:14])[CH2:12][CH2:11][CH2:10]2)=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 529835861-(4-Fluorophenyl)cyclobutan-1-amine hydrochlorideHCID 673587022-(2-Oxo-3-phenylpiperidin-1-yl)acetic acid

Product 1

HCID 45275499N-[1-(4-fluorophenyl)cyclobutyl]-2-(2-oxo-3-phenylpiperidin-1-yl)acetamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(4-fluorophenyl)cyclobutanamine hydrochloride (0.048 g, 0.236 mmol) and 2-(2-oxo-3-phenylpiperidin-1-yl)acetic acid (Example 91D, 0.050 g, 0.214 mmol) in dichloromethane (0.5 mL) was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.049 mL, 0.279 mmol) (0.049 mL, 0.279 mmol), and the reaction was stirred for approximately 60 hours. The reaction was loaded directly onto a SF15-12 silica gel column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 5% to 100% ethyl acetate/hexanes over 20 minutes (flow=30 mL/minute). The product was dissolved in a minimal ethyl acetate and hexanes was added which caused the product to precipitate from solution. Concentration gave the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.34-7.43 (m, 2H), 7.22-7.34 (m, 3H), 7.14-7.20 (m, 2H), 7.09-7.11 (br s, 1H), 6.97-7.03 (m, 2H), 4.03 (d, J=14.1 Hz, 1H), 3.87 (d, J=14.1 Hz, 1H), 3.69 (dd, J=7.9, 6.0 Hz, 1H), 3.51-3.60 (m, 1H), 3.39-3.48 (m, 1H), 2.47-2.60 (m, 4H), 1.78-2.17 (m, 6H); MS (ESI−) m/z 379 (M−H)−.

Workup

  1. washthe title compound was eluted
  2. customover 20 minutes
  3. dissolutionThe product was dissolved in a minimal ethyl acetate and hexanes
  4. additionwas added which
  5. customto precipitate from solution
  6. concentrationConcentration

Sources & evidence

ORD record
ord-08c21fc3817b427aa6caf4e6e54408f8
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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