Triethylamine → 1-(6-Fluoro-1,2,3,4-tetrahydroisoquinolin-2-yl)-2-[[4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl]oxy]ethan-1-one

HRID 1772275Notes

Reaction equation

HRID 1772275 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][CH:11]2[CH2:16][CH2:15][CH:14]([O:17][CH2:18][C:19](O)=[O:20])[CH2:13][CH2:12]2)=[CH:6][C:5]=1[C:22]([F:25])([F:24])[F:23])([O-:3])=[O:2].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[F:55][C:56]1[CH:57]=[C:58]2[C:63](=[CH:64][CH:65]=1)[CH2:62][NH:61][CH2:60][CH2:59]2>ClCCl.O>[F:55][C:56]1[CH:57]=[C:58]2[C:63](=[CH:64][CH:65]=1)[CH2:62][N:61]([C:19](=[O:20])[CH2:18][O:17][CH:14]1[CH2:13][CH2:12][CH:11]([NH:10][C:7]3[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[C:5]([C:22]([F:23])([F:25])[F:24])[CH:6]=3)[CH2:16][CH2:15]1)[CH2:60][CH2:59]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 157187246-Fluoro-1,2,3,4-tetrahydroisoquinolineHCID 672837722-(4-(4-Nitro-3-(trifluoromethyl)phenylamino)cyclohexyloxy)acetic acid

Product 1

HCID 867195131-(6-Fluoro-1,2,3,4-tetrahydroisoquinolin-2-yl)-2-[[4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl]oxy]ethan-1-oneYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-[[4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl]oxy]acetic acid (144 mg, 0.40 mmol) in dichloromethane (15 ml) was added EDAC.HCl (114 mg, 0.59 mmol), HOBt (80 mg, 0.59 mmol) and triethylamine (120 mg, 1.19 mmol) with stirring for 30 minutes. Then 6-fluoro-1,2,3,4-tetrahydroisoquinoline (60 mg, 0.40 mmol) was added to the reaction mixture and the contents were stirred overnight at room temperature. The reaction mixture was diluted with water (100 ml) and extracted with dichloromethane (3×80 ml). The organic fractions were combined, dried over anhydrous sodium sulfate, filtered, and evaporated to give a residue, which was purified by silica gel column chromatography using 5% ethyl acetate in dichloromethane to afford 1-(6-fluoro-1,2,3,4-tetrahydroisoquinolin-2-yl)-2-[[4-[[4-nitro-3-(trifluoromethyl)phenyl]amino]cyclohexyl]oxy]ethan-1-one as a yellow solid (93.8 mg, 48%); (ES, m/z): [M+H]+ 496.00; 1H NMR (300 MHz, CDCl3): δ 8.01 (d, J=9.0 Hz, 1H), 7.09 (m, 1H), 6.95-6.82 (m, 3H), 6.65 (d, J=9.0 Hz, 1H), 4.69 (m, 2H), 4.28 (s, 2H), 3.84-3.70 (m, 2H), 3.48-3.33 (m, 2H), 2.93-2.83 (m, 2H), 2.16-2.13 (m, 4H), 1.52-1.40 (m, 2H), 1.34-1.16 (m, 2H).

Workup

  1. stirringthe contents were stirred overnight at room temperature
  2. extractionextracted with dichloromethane (3×80 ml)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customto give a residue, which
  7. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-5f6663856f964164bda47716a3a4d6ef
Source dataset
uspto-grants-2016_02
Patent number
US09249102B2

Reaction notes

Loading…