1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}-3-phenylpiperidin-2-one

HRID 1667182Notes

Reaction equation

HRID 1667182 reaction equation
Cl.[F:2][C:3]([F:15])([F:14])[C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][NH:10][CH2:11]2)=[CH:6][CH:5]=1.[O:16]=[C:17]1[CH:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19][N:18]1[CH2:29][C:30](O)=[O:31].C(N=C=NCCCN(C)C)C>ClCCl>[O:31]=[C:30]([N:10]1[CH2:9][CH2:8][C:7]2[C:12](=[CH:13][C:4]([C:3]([F:2])([F:14])[F:15])=[CH:5][CH:6]=2)[CH2:11]1)[CH2:29][N:18]1[CH2:19][CH2:20][CH2:21][CH:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]1=[O:16]

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 441182867-(Trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline hydrochlorideHCID 673587022-(2-Oxo-3-phenylpiperidin-1-yl)acetic acid

Product 1

HCID 452755001-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]ethyl}-3-phenylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline hydrochloride (0.056 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), and the reaction was stirred for approximately 39 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/hexane over 20 minutes (flow=30 mL/minute). The product was dissolved in a minimal amount of ethyl acetate, and hexanes were added which caused the product to precipitate. Concentration gave the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.16-7.48 (m, 8H), 4.80 (s, 1H), 4.71 (s, 1H), 4.48-4.57 (m, 1H), 4.09-4.23 (m, 1H), 3.78-3.99 (m, 1H), 3.68-3.79 (m, 2H), 3.54-3.67 (m, 1H), 3.40-3.54 (m, 1H), 2.90-3.03 (m, 2H), 2.13-2.30 (m, 1H), 1.93-2.11 (m, 2H), 1.76-1.96 (m, 1H); MS (ESI+) m/z 417 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-e122c10ead624a4ca07871534e5f1dec
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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