Methyl bromoacetate → (1Z)-1-[3-(2-butan-2-ylphenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]urea

HRID 59857Notes

Reaction equation

HRID 59857 reaction equation
[CH:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11][C:12]([NH2:14])=[S:13])([CH2:3][CH3:4])[CH3:2].Br[CH2:16][C:17](OC)=[O:18].[N+](C1C=CC([N:30]([C:34]2[CH:39]=[CH:38][C:37]([C:40]3[N:44]=[CH:43][N:42]([C:45]4[CH:50]=[CH:49][C:48]([O:51][C:52]([F:55])([F:54])[F:53])=[CH:47][CH:46]=4)[N:41]=3)=[CH:36][CH:35]=2)[C:31](=O)[O-:32])=CC=1)([O-])=O.CCN(C(C)C)C(C)C>CC(C)=O.C(OCC)C>[CH:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[C:17](=[O:18])[CH2:16][S:13]/[C:12]/1=[N:14]\[C:31]([NH:30][C:34]1[CH:39]=[CH:38][C:37]([C:40]2[N:44]=[CH:43][N:42]([C:45]3[CH:50]=[CH:49][C:48]([O:51][C:52]([F:53])([F:54])[F:55])=[CH:47][CH:46]=3)[N:41]=2)=[CH:36][CH:35]=1)=[O:32])([CH2:3][CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 86675797HCID 86675797, compoundHCID 1182234684-nitrophenyl(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)carbamate

Product 1

HCID 89373153(1Z)-1-[3-(2-butan-2-ylphenyl)-4-oxo-1,3-thiazolidin-2-ylidene]-3-[4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]phenyl]ureaYield 102.3%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 1-(2-(sec-butyl)phenylthiourea (1.40 g, 6.72 mmol) suspended in 5 mL of acetone was added methyl bromoacetate (1.23 g, 1.20 mmol), and the solution was allowed to stir at ambient temperature for 18 h. The solution was then diluted with 8 mL of diethyl ether and, after stirring for 30 min, the solvent was carefully decanted from a gummy oil. The intermediate, methyl 2-((N-(2-(sec-butyl)phenyl)carbamimidoyl)thio)acetate HBr (B8), was dissolved in 8 mL of dry tetrahydrofuran and 4-nitrophenyl(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)carbamate (3.26 g, 6.72 mmol) was added, followed by Hünig's base (2.6 g, 20 mmol). The solution was allowed to stir at ambient temperature for 3 h, then it was concentrated and the residue chromatographed (silica gel, 0-70% EtOAc-hexanes) to give 730 mg (18%) of the title compound as a solid, mp 169-177° C.; 1H NMR (400 MHz, CDCl3) δ 8.53 (s, 1H), 8.12 (d, J=8.7 Hz, 2H), 7.81-7.74 (m, 2H), 7.63-7.56 (m, 2H), 7.52 (m, 1H), 7.45 (d, J=7.9 Hz, 1H), 7.41-7.32 (m, 3H), 7.28 (s, 1H), 7.11 (d, J=7.9 Hz, 1H), 4.03-3.95 (m, 2H), 2.43 (dd, J=13.5, 6.8 Hz, 1H), 1.73-1.56 (m, 2H), 1.20 (overlapping d, J=7.6 Hz, 3H), 0.78 (overlapping t, J=7.4 Hz, 3H); ESIMS m/z 594 ([M+H]+).

Workup

  1. stirringafter stirring for 30 min
  2. customthe solvent was carefully decanted from a gummy oil
  3. dissolutionThe intermediate, methyl 2-((N-(2-(sec-butyl)phenyl)carbamimidoyl)thio)acetate HBr (B8), was dissolved in 8 mL of dry tetrahydrofuran
  4. stirringto stir at ambient temperature for 3 h
  5. concentrationit was concentrated
  6. customthe residue chromatographed (silica gel, 0-70% EtOAc-hexanes)

Sources & evidence

ORD record
ord-9e200dd1490541fb828fea01262cc13a
Source dataset
uspto-grants-2016_09
Patent number
US09440964B2

Reaction notes

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