Dimethyl Sulfoxide → 4-[3-Methyl-1-(7-methyl-quinoline-3-ylamino)-butyl]-benzoic acid ethyl ester

HRID 2281147Notes

Reaction equation

HRID 2281147 reaction equation
[NH2:1][CH:2]([C:6]1[CH:16]=[CH:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][CH:7]=1)[CH2:3][CH2:4][CH3:5].Br[C:18]1[CH:19]=[N:20][C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[C:23]([CH3:28])[CH:22]=2.[CH3:29]S(C)=O>[Cu]I>[CH2:13]([O:12][C:10](=[O:11])[C:9]1[CH:15]=[CH:16][C:6]([CH:2]([NH:1][C:18]2[CH:19]=[N:20][C:21]3[C:26]([CH:27]=2)=[CH:25][CH:24]=[C:23]([CH3:28])[CH:22]=3)[CH2:3][CH:4]([CH3:29])[CH3:5])=[CH:7][CH:8]=1)[CH3:14]

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 124656213-Bromo-7-methylquinolineHCID 71243833Ethyl(+/-)-4-(1-aminobutyl)benzoate

Product 1

HCID 712393454-[3-Methyl-1-(7-methyl-quinoline-3-ylamino)-butyl]-benzoic acid ethyl esterYield 15%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

To a reaction vial with 4-(1-Amino-3-methyl-butyryl)-benzoic acid ethyl ester (2) (440 mg, 1.9 mM) was added DMSO (6.33 mL), 3-bromo-7-methylquinoline (9) (420 mg, 1.9 mM), followed by CuI catalyst (36 mg, 0.19 mM) and CsOAc (726 mg, 3.78 mM). The mixture was purged with argon gas and then the tube was sealed. The reaction mixture was heated to 100° for 48 h. The reaction mixture was cooled, diluted with EtOAc (10 mL), washed with water (3×5 mL), dried (Na2SO4) and concentrated. The crude material was separated by a 40 g silica gel with 0-80% EtOAc in heptane to give a yellow color product (108 mg, 15%). 1H NMR (500 MHz, CDCl3) δ ppm 0.98 (d, J=6.34 Hz, 3 H) 1.04 (d, J=6.34 Hz, 3 H) 1.39 (t, 3 H) 1.61-1.71 (m, 1 H) 1.71-1.86 (m, 2 H) 2.46 (s, 3 H) 4.36 (q, 2 H) 4.38-4.43 (m, 1 H) 4.47-4.56 (m, 1 H) 6.75 (d, J=1.95 Hz, 1 H) 7.20 (d, J=8.29 Hz, 1 H) 7.36 (d, J=8.05 Hz, 1 H) 7.47 (d, J=8.29 Hz, 2 H) 7.69 (s, 1 H) 8.03 (d, 2 H) 8.47 (br. s., 1 H). LC-MS: m/z 377.2 (M+1).

Workup

  1. customThe mixture was purged with argon gas
  2. customthe tube was sealed
  3. temperatureThe reaction mixture was heated to 100° for 48 h
  4. temperatureThe reaction mixture was cooled
  5. additiondiluted with EtOAc (10 mL)
  6. washwashed with water (3×5 mL)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe crude material was separated by a 40 g silica gel with 0-80% EtOAc in heptane

Sources & evidence

ORD record
ord-3ebbc65aa10c428fa6b27c977260e1c6
Source dataset
uspto-grants-2015_09
Patent number
US09139538B2

Reaction notes

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