1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → HCID 178523897, compound

HRID 2280404Notes

Reaction equation

HRID 2280404 reaction equation
[Cl:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[CH2:4][NH:5][C:6]([NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]([F:17])[CH:11]=1)=S.[NH2:24][C:25]1[NH:29][N:28]=[C:27]([C:30]([F:33])([F:32])[F:31])[CH:26]=1.Cl.C(N=C=NCCCN(C)C)C>C1COCC1.O.C(OC(C)C)(=O)C>[Cl:1][C:2]1[CH:22]=[C:21]([F:23])[CH:20]=[CH:19][C:3]=1[CH2:4][NH:5]/[C:6](/[NH:24][C:25]1[NH:29][N:28]=[C:27]([C:30]([F:33])([F:32])[F:31])[CH:26]=1)=[N:8]/[C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]([F:17])[CH:11]=1

Participants

7

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86704068HCID 86704068, compoundHCID 178507669HCID 178507669, compound

Product 1

HCID 178523897HCID 178523897, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 7915Isopropyl AcetateSolventHCID 8028TetrahydrofuranSolvent

Procedure

N-((2-Chloro-4-fluorobenzyl)carbamothioyl)-3,4-difluorobenzamide (98.0 g, 273 mmol) and 5-amino-3-trifluoromethylpyrazole (41.3 g, 273 mmol) were dissolved in THF (546 mL). N1-((Ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (57.6 g, 300 mmol) was added and the reaction was stirred at room temperature for 1 h and then heated to 40° C. for 15 h. The crude mixture was diluted with water (500 mL) and isopropyl acetate (500 mL). The organic layer was washed with brine (500 mL), dried over sodium sulfate, and concentrated. The residue was diluted with isopropyl acetate (1.3 L) and heated to 65° C. for 1 hour. The solution was allowed to cool to room temperature, filtered and the filtrate was concentrated. The residue was heated to 70° C. in acetonitrile (900 mL) and then allowed to cool to room temperature. The resulting suspension was filtered, rinsed with acetonitrile (200 mL) and dried in vacuo at 60° C. to afford 55 g (43%) of (Z)—N-(((2-chloro-4-fluorobenzyl)amino)((3-(trifluoromethyl)-1H-pyrazol-5-yl)amino)methylene)-3,4-difluorobenzamide as a white solid. 1HNMR (400 MHz, MeOH-d4) δ 7.95 (bs, 2H), 7.50 (t, 1H, J=7.2 Hz), 7.26 (m, 2H), 7.06 (t, 1H, J=7.5 Hz), 6.56 (s, 1H), 4.84 (s, 2H).

Workup

  1. temperatureheated to 40° C. for 15 h
  2. washThe organic layer was washed with brine (500 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. additionThe residue was diluted with isopropyl acetate (1.3 L)
  6. temperatureheated to 65° C. for 1 hour
  7. temperatureto cool to room temperature
  8. filtrationfiltered
  9. concentrationthe filtrate was concentrated
  10. temperatureThe residue was heated to 70° C. in acetonitrile (900 mL)
  11. temperatureto cool to room temperature
  12. filtrationThe resulting suspension was filtered
  13. washrinsed with acetonitrile (200 mL)
  14. customdried in vacuo at 60° C.

Sources & evidence

ORD record
ord-7ff417b845d24533afac23a99837d194
Source dataset
uspto-grants-2015_09
Patent number
US09139532B2

Reaction notes

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