Triethylamine → 1-(3-(4-Fluoro-3-methoxyphenyl)-3-methyl-2-oxobutyl)-3-(4-fluorophenyl)thiourea

HRID 1627349Notes

Reaction equation

HRID 1627349 reaction equation
Cl.[NH2:2][CH2:3][C:4](=[O:17])[C:5]([C:8]1[CH:13]=[CH:12][C:11]([F:14])=[C:10]([O:15][CH3:16])[CH:9]=1)([CH3:7])[CH3:6].[F:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]=[C:26]=[S:27])=[CH:21][CH:20]=1.CCN(CC)CC>C(Cl)Cl>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]([CH3:7])([CH3:6])[C:4](=[O:17])[CH2:3][NH:2][C:26]([NH:25][C:22]2[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=2)=[S:27])=[CH:9][C:10]=1[O:15][CH3:16]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 152414-Fluorophenyl isothiocyanateHCID 667407491-Amino-3-(4-fluoro-3-methoxyphenyl)-3-methylbutan-2-one hydrochloride

Product 1

HCID 866622481-(3-(4-Fluoro-3-methoxyphenyl)-3-methyl-2-oxobutyl)-3-(4-fluorophenyl)thioureaYield 88.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 1-amino-3-(4-fluoro-3-methoxyphenyl)-3-methylbutan-2-one hydrochloride (35.4 g, 0.135 mol) and 4-fluorophenyl isothiocyanate (21.75 g, 0.142 mol) in DCM (500 mL) was added Et3N (37.6 ml, 0.27 mol) at 0° C., and the reaction mixture was warm to room temperature over 1 h. The reaction mixture was washed with 1N HCl (500 mL), satd NaHCO3 (500 mL) and brine (500 mL) successively, dried over MgSO4, filtered and concentrated under reduced pressure give a residue, which was triturated with Hex-EtOAc to afford 1-(3-(4-fluoro-3-methoxyphenyl)-3-methyl-2-oxobutyl)-3-(4-fluorophenyl)thiourea (45 g, 88%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.85 (b, 1H), 7.25 (m, 2H), 7.15 (m, 2H), 7.05 (m, 1H), 6.79 (m, 2H), 6.67 (b, 1H), 3.88 (s, 3H), 1.54 (s, 6H).

Workup

  1. washThe reaction mixture was washed with 1N HCl (500 mL), satd NaHCO3 (500 mL) and brine (500 mL) successively
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customgive a residue, which
  6. customwas triturated with Hex-EtOAc

Sources & evidence

ORD record
ord-b6a501d27bd54c2b9863f439856fdda6
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

Loading…