Triethylamine → Ethyl 4-{(1S)-1-[3-(3,5-dichlorophenyl)-5-(7-methoxyquinolin-3-yl)-1H-pyrazol-1-yl]ethyl}benzoate

HRID 1865426Notes

Reaction equation

HRID 1865426 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]#[C:10][C:11]([C:13]2[CH:14]=[N:15][C:16]3[C:21]([CH:22]=2)=[CH:20][CH:19]=[C:18]([O:23][CH3:24])[CH:17]=3)=O)[CH:5]=[C:6]([Cl:8])[CH:7]=1.Cl.[NH:26]([C@H:28]([C:30]1[CH:40]=[CH:39][C:33]([C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:32][CH:31]=1)[CH3:29])[NH2:27].C(N(CC)CC)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[C:11]([C:13]3[CH:14]=[N:15][C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[C:18]([O:23][CH3:24])[CH:17]=4)[N:26]([C@H:28]([C:30]3[CH:40]=[CH:39][C:33]([C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:32][CH:31]=3)[CH3:29])[N:27]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 67484658ethyl 4-[(1S)-1-hydrazinoethyl]benzoate hydrochlorideHCID 674869013-(3,5-Dichlorophenyl)-1-(7-methoxyquinolin-3-yl)prop-2-yn-1-one

Product 1

HCID 68567756Ethyl 4-{(1S)-1-[3-(3,5-dichlorophenyl)-5-(7-methoxyquinolin-3-yl)-1H-pyrazol-1-yl]ethyl}benzoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the intermediate from step F (118 mg, 0.33 mmol) in DMF was added the ethyl 4-[(1S)-1-hydrazinoethyl]benzoate hydrochloride (89 mg, 0.36 mmol) and triethyl amine (55 μL, 0.39 mmol). After stirring the reaction mixture at room temperature for 18 hours it was concentrated in vacuo. The residue was diluted with water and ethyl acetate. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography using 25% ethyl acetate-hexanes. This material was then re-purified with 3% acetonitrile-dichloromethane to give the desired compound. 1H NMR (500 MHz, CDCl3): 8.76 (d, J=2.0 Hz, 1H), 8.04 (d, J=8.2 Hz, 2H), 7.92 (1.8 Hz, 1H), 7.85 (d, J=1.8 Hz, 2H), 7.68 (d, J=8.9 Hz, 1H), 7.5 (d, J=2.1 Hz, 1H), 7.36 (t, J=1.8 Hz, 1H), 7.31 (d, J=8.0 Hz, 2H), 6.76 (s, 1H), 4.42 (q, J=7.0 Hz, 1H), 4.03 (s, 3H), 2.04 (s, 3H), 2.01 (t, J=7.1 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H). LC-MS: 4.28 min; (M+H)=546.0.

Workup

  1. concentrationwas concentrated in vacuo
  2. additionThe residue was diluted with water and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography
  8. customThis material was then re-purified with 3% acetonitrile-dichloromethane

Sources & evidence

ORD record
ord-c9f155fc340149d58675e8bdb6302682
Source dataset
uspto-grants-2009_12
Patent number
US07625938B2

Reaction notes

Loading…