1,2-Dichloroethane → 4-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxo-N-(3-(trifluoromethyl)benzyl)butyric acid amide

HRID 383996Notes

Reaction equation

HRID 383996 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:18](=[O:24])[CH2:19][CH2:20][C:21](O)=[O:22])[CH:9]2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1.[F:25][C:26]([F:36])([F:35])[C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH2:30][NH2:31].C1C=NC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl.CO.CCCCCCC.O>[NH3:8].[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:18](=[O:24])[CH2:19][CH2:20][C:21]([NH:31][CH2:30][C:29]3[CH:32]=[CH:33][CH:34]=[C:27]([C:26]([F:35])([F:36])[F:25])[CH:28]=3)=[O:22])[CH:9]2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:4][CH:3]=1

Participants

10

Reactant 4

HCID 111,2-DichloroethaneHCID 759623-(Trifluoromethyl)benzylamineHCID 181649HOAtHCID 685597314-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyric acid

Product 2

HCID 222AmmoniaYield 2%HCID 468297284-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxo-N-(3-(trifluoromethyl)benzyl)butyric acid amideYield 163.9%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8900HeptaneSolvent

Procedure

A solution of 200 mg (0.61 mmol) of 4-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxobutyric acid (intermediate VVV04) and 88.0 μl (0.61 mmol) of 3-trifluoromethyl benzylamine in DCM (15 ml) was cooled to 0° C. and then 8.3 mg (0.06 mmol) of HOAt and 129 mg (0.67 mmol) of EDC were added in succession. The mixture was then stirred for 16 h at room temperature. The reaction solution was poured into water (75 ml) and extracted with DCM (2×75 ml). The combined organic phases were washed with a 1M aqueous NaOH solution (100 ml) and brine, dried over Na2SO4, filtered and concentrated to small volume under vacuum. Column chromatography (heptane/EE 1:1+2% 7N NH3 in MeOH) of the residue produced 240 mg (0.50 mmol, 81%) of 4-(7-fluoro-1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl)-4-oxo-N-(3-(trifluoromethyl)benzyl)butyric acid amide. MS: m/z 485.2 [M+H]+.

Workup

  1. extractionextracted with DCM (2×75 ml)
  2. washThe combined organic phases were washed with a 1M aqueous NaOH solution (100 ml) and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to small volume under vacuum

Sources & evidence

ORD record
ord-a1028a73f5a247e3906eb55230a3b1a3
Source dataset
uspto-grants-2013_02
Patent number
US08367700B2

Reaction notes

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