Stannous Chloride → HCID 86683695, compound

HRID 1525684Notes

Reaction equation

HRID 1525684 reaction equation
[N:1]([O-])=O.[Na+].[NH2:5][C:6]1[CH:15]=[CH:14][C:9]([C:10]([NH:12][CH3:13])=[O:11])=[C:8]([F:16])[CH:7]=1.Cl[Sn]Cl>Cl>[NH:5]([C:6]1[CH:15]=[CH:14][C:9]([C:10]([NH:12][CH3:13])=[O:11])=[C:8]([F:16])[CH:7]=1)[NH2:1]

Participants

5

Reactant 3

HCID 24479Stannous ChlorideHCID 23668193Sodium NitriteHCID 441395214-Amino-2-fluoro-N-methylbenzamide

Product 1

HCID 86683695HCID 86683695, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent2×

Procedure

2.5M Solution of NaNO2 (2.38 ml) was added dropwise to a solution of 4-amino-N-methyl-2-fluorobenzamide (1 g, 5.95 mmol) in B 5N HCl (3.1 ml), so that the temperature of the reaction mixture did not exceed 5° C. The mixture was stirred for additional 30 min at the same temperature, after that the prepared solution was added drop by drop to a suspension of SnCl2*2H2O (4.03 g, 17.9 mmol) in HCl (4.2 ml) at 0° C., and stirring was continued for 2 h at the same temperature. Precipitated solid was filtered off, dissolved in water (40 ml) and NaOH was added to strongly basic reaction. The mixture was extracted with ether (3*100 ml), dried over MgSO4 and evaporated in vacuo. It gave 4-hydrazino-N-methyl-2-fluorobenzamide 7 (R1=CH3). LCMS (M+H)+ 184. 1H NMR (CDCl3, 400 MHz): 7.96 (t, J=8.4 Hz, 1H), 6.64 (br. m, 1H), 6.60 (t, J=1.6 Hz, 1H), 6.57 (dd, J1=7.2 Hz, J2=2.0 Hz, 1H), 5.60 (br. s, 1H), 3.66 (br. s, 2H), 3.00 (dd, J1=4.8 Hz, J2=1.2 Hz, 1H). The solution of 4-isocyanato-2-(trifluoromethyl)benzonitrile (59 mg, 0.27 mmol) 3.1 in dioxane (2 ml) was added to a solution of 4-hydrazino-N-methyl-2-fluorobenzamide (54 mg, 0.29 mmol) 7 in dioxane (3 ml), and the resultant mixture was stirred for 2 h. Then dioxane was distilled in vacuo, the residue was crumbled with ether, filtered off and dried in vacuo. It gave 2-[(4-methylcarbamoyl)-3-fluorophenyl]-N-[3-(trifluoromethyl)-4-cyanophenyl]-hydrazine carboxamide 8(1) (R1=CH3). LCMS (M+H)+ 405. 1H NMR (DMSO-d6, 400 MHz): 9.65 (br. s, 1H), 8.72 (br. s, 1H), 8.37 (s, 1H), 8.25 (br. s, 1H), 8.03 (br. m, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.58 (m, 2H), 6.63 (d, J=8.4 Hz, 1H), 6.48 (d, J=14.0 Hz, 1H), 2.77 (d, J=4.4 Hz, 3H). Triethylamine (56 mkl, 0.4 mmol) and diphosgene (27 mkl, 0.22 mmol) were added one after another to 2-[(4-methylcarbamoyl)-3-fluorophenyl]-N-[3-(trifluoromethyl)-4-cyanophenyl]-hydrazine carboxamide (80 mg, 0.2 mmol) 8(1) in dichloroethane (2 ml). The reaction mixture was stirred in a closed vial at 80° C. for 15 h. The solvent was evaporated in vacuo and the residue was subjected to chromatography on SiO2 (eluent—CH2Cl2:MeOH, gradient from 100:1 till 20:1). It gave N-methyl-2-fluoro-4-[4-[3-(trifluoromethyl)-4-cyanophenyl]-3,5-dioxo-1,2,4-triazolidin-1-yl]benzamide 1.4 (R1=CH3). Ki1.4=55.2 nM, LCMS (M+H)+ 422. 1H NMR (DMSO-d6, 400 MHz): 11.53 (s, 1H), 8.22 (br. m, 1H), 8.16 (d, J=8.8 Hz, 1H), 7.99 (dd, J1=8.8 Hz, J2=1.6 Hz, 1H), 7.95 (d, J=1.6 Hz, 1H), 7.81 (t, J=8.4 Hz, 1H), 7.69 (dd, J1=8.8 Hz, J2=2.0 Hz, 1H), 7.62 (dd, J1=12.0 Hz, J2=2.0 Hz, 1H), 2.79 (d, J=4.4 Hz, 3H).

Workup

  1. customdid not exceed 5° C
  2. additionafter that the prepared solution was added drop by drop
  3. stirringstirring
  4. waitwas continued for 2 h at the same temperature
  5. customPrecipitated solid
  6. filtrationwas filtered off
  7. dissolutiondissolved in water (40 ml)
  8. additionNaOH was added to strongly basic reaction
  9. extractionThe mixture was extracted with ether (3*100 ml)
  10. dry with materialdried over MgSO4
  11. customevaporated in vacuo

Sources & evidence

ORD record
ord-297eae5323df4b2da332aaeb9bde260a
Source dataset
uspto-grants-2015_07
Patent number
US09085539B2

Reaction notes

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