Sodium Hydroxide → HCID 58367173, compound

HRID 1891444Notes

Reaction equation

HRID 1891444 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[F:12])[C:6](O)=O)#[N:2].[NH2:13][NH:14][C:15]([NH2:17])=[S:16].O=P(Cl)(Cl)Cl.[OH-].[Na+]>O.CC(=O)OCC>[NH2:17][C:15]1[S:16][C:6]([C:5]2[CH:9]=[CH:10][C:11]([F:12])=[C:3]([CH:4]=2)[C:1]#[N:2])=[N:13][N:14]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 2723789ThiosemicarbazideHCID 27739323-Cyano-4-fluorobenzoic acid

Product 1

HCID 58367173HCID 58367173, compoundYield 52.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred mixture of 3-cyano-4-fluorobenzoic acid (37.3 g, 225 mmol) and thiosemicarbazide (22.6 g, 248 mmol) was added POCl3 (148 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 h and then heated to 85° C. for 6 h. The resulting yellow solution was cooled to room temperature and concentrated to 50% volume. The residue was cooled to 0° C. and water was added (300 mL) drop wise. (Caution: exothermic and violent reaction with gas evolution). The mixture was heated to 90° C. for 1 h then cooled to room temperature. EA was added EA (300 mL) and the reaction mixture stirred for 10 min and before filtration. The collected solid was dispersed into water (270 mL), cooled to 0° C., and neutralized with 50% NaOH aqueous solution to pH8. The resulting solid was filtered, washed thoroughly with water, and dried under high vacuum to afford 26 g (52%) of 5-(5-amino-1,3,4-thiadiazol-2-yl)-2-fluorobenzonitrile TDZ INT-1 as pale yellow solid which was used in next experiment without purification. LCMS-ESI (m/z) calculated for C9H5FN4S: 220.0; found 221.1 [M+H]+, tR=2.44 min. 1H NMR (400 MHz, DMSO) δ 8.29 (dd, J=6.1, 2.3 Hz, 1H), 8.19 (ddd, J=8.9, 5.2, 2.4 Hz, 1H), 7.64 (t, J=9.0 Hz, 1H), 7.58 (s, 2H). 13C NMR (101 MHz, DMSO) δ 169.82, 164.25, 161.68, 133.68, 131.65, 128.96, 117.96, 113.77, 101.59.

Workup

  1. temperatureheated to 85° C. for 6 h
  2. temperatureThe resulting yellow solution was cooled to room temperature
  3. concentrationconcentrated to 50% volume
  4. temperatureThe residue was cooled to 0° C.
  5. additionwater was added (300 mL) drop wise
  6. custom(Caution: exothermic and violent reaction with gas evolution)
  7. temperatureThe mixture was heated to 90° C. for 1 h
  8. temperaturethen cooled to room temperature
  9. stirringthe reaction mixture stirred for 10 min and before filtration
  10. temperaturecooled to 0° C.
  11. filtrationThe resulting solid was filtered
  12. washwashed thoroughly with water
  13. customdried under high vacuum

Sources & evidence

ORD record
ord-90e16a7fe49e4fafb94fb21da01a842a
Source dataset
uspto-grants-2013_08
Patent number
US08507538B2

Reaction notes

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