Water → HCID 50923390, compound

HRID 1752166Notes

Reaction equation

HRID 1752166 reaction equation
BrBr.[Cl:3][C:4]1[CH:5]=[C:6]([NH:11][C:12]([N:14]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)[C:15]([NH2:17])=[O:16])=[S:13])[CH:7]=[CH:8][C:9]=1[Cl:10].O>CCO>[Cl:3][C:4]1[CH:5]=[C:6]([N:11]=[C:12]2[S:13][NH:17][C:15](=[O:16])[N:14]2[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:27])([F:28])[F:26])[CH:20]=2)[CH:7]=[CH:8][C:9]=1[Cl:10]

Participants

5

Reactant 3

HCID 962WaterHCID 24408BromineHCID 86667922HCID 86667922, compound

Product 1

HCID 50923390HCID 50923390, compoundYield 103.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Bromine (16 mg in 0.5 mL of EtOH) was added dropwise to a solution of 1-[(3,4-dichlorophenyl)carbamothioyl]-1-[[3-(trifluoromethyl)phenyl]methyl]urea (42 mg, 0.1 mmol) in 0.5 mL EtOH at 0° C. HPLC-MS analysis revealed almost complete conversion to product after 30 min of stirring. The reaction was worked up after 1.5 h. Water (3 mL) was added and the resulting aqueous phase was extracted with Et2O (3×15 mL). The combined organic phases were washed with brine, dried over Na2SO4 and concentrated in vacuo to yield 43.5 mg of crude material (approximately 90% purity). The material was purified by preparative HPLC (basic conditions) XTerra Prep MS C18 5 mm 19×50 mm column, flow 25 ml/min, 50 mM pH10 NH4HCO3/ACN, 5-97% ACN in 6 min, fractions collected based on UV-signal (254 nm) to give the product in 21.7 mg (52%). HPLC purity: 98.5%, MS: m/z: 420 (M+H), 1H NMR (500 MHz, Chloroform-d) 8 ppm 7.81 (s, 1 H) 7.70 (d, J=7.81 Hz, 1 H) 7.60 (d, J=7.81 Hz, 1 H) 7.49 (t, J=7.69 Hz, 1 H) 7.40 (d, J=8.55 Hz, 1 H) 7.06 (d, J=2.44 Hz, 1 H) 6.79 (dd, J=8.55, 2.44 Hz, 1 H) 5.04 (s, 2 H).

Workup

  1. customafter 30 min
  2. extractionthe resulting aqueous phase was extracted with Et2O (3×15 mL)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7306d6a45633414ea1aada18dcf9891f
Source dataset
uspto-grants-2015_10
Patent number
US09162994B2

Reaction notes

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