Hydrochloric Acid → 1-(3-Methyl-2-(phenylamino)quinolin-8-yl)ethanone

HRID 1055930Notes

Reaction equation

HRID 1055930 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:8]([CH3:19])=[CH:7]2.C([Sn](CCCC)(CCCC)[C:25]([O:27]CC)=[CH2:26])CCC.Cl.CCN(CC)CC>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][C:8]1[C:9]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[N:10][C:11]2[C:6]([CH:7]=1)=[CH:5][CH:4]=[CH:3][C:2]=2[C:25](=[O:27])[CH3:26]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 897822388-bromo-3-methyl-N-phenylquinolin-2-amine

Product 1

HCID 897818941-(3-Methyl-2-(phenylamino)quinolin-8-yl)ethanoneYield 100.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 8-bromo-3-methyl-N-phenylquinolin-2-amine (182.0 mg, 0.581 mmol), tributyl(1-ethoxyvinyl)stannane (Synthonix, Inc., Wake Forest, N.C.; 0.216 mL, 0.639 mmol), and Pd(PPh3)4 (33.6 mg, 0.029 mmol) in toluene (3.0 mL) was sparged with argon and stirred under argon at 100° C. for 16 h. The mixture was then concentrated in vacuo, and the residue was taken up in THF (3.0 mL). HCl (concentrated, aq.; 0.073 mL, 0.872 mmol) was added, and the resulting mixture was stirred at 60° C. for 15 min. Et3N (0.243 mL, 1.743 mmol) was added, and the mixture was concentrated onto silica gel. Chromatographic purification (silica gel, 0-50% EtOAc/hexanes) furnished 1-(3-methyl-2-(phenylamino)quinolin-8-yl)ethanone (161 mg, 0.583 mmol, 100% yield) as a yellow oil: 1H NMR (400 MHz, CD Cl3) δ ppm 7.79 (1H, s), 7.76 (1H, d, J=7.2 Hz), 7.64-7.72 (3H, m), 7.38 (2H, t, J=7.8 Hz), 7.29 (1H, t, J=7.5 Hz), 7.11 (1H, t, J=7.4 Hz), 6.52 (1H, br. s.), 2.76 (3H, s), 2.44 (3H, s). m/z (ESI, +ve) 277.1 (M+H)+.

Workup

  1. concentrationThe mixture was then concentrated in vacuo
  2. stirringthe resulting mixture was stirred at 60° C. for 15 min
  3. concentrationthe mixture was concentrated onto silica gel
  4. customChromatographic purification (silica gel, 0-50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b73468c332ab4689b87597762fdbd7cc
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…