Hydrazine → 5-(4-chloro-1-(4-fluorophenyl)butyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine

HRID 1803235Notes

Reaction equation

HRID 1803235 reaction equation
C(N(C(C)C)C(C)C)C.I.[F:11][C:12]1[CH:13]=[C:14]([NH:24][C:25](SC)=[NH:26])[CH:15]=[CH:16][C:17]=1[N:18]1[C:22]([CH3:23])=[N:21][CH:20]=[N:19]1.[F:29][C:30]1[CH:35]=[CH:34][C:33]([CH:36]([CH2:40][CH:41]=[CH2:42])[C:37](O)=O)=[CH:32][CH:31]=1.O.ON1C2C=CC=CC=2N=N1.[ClH:54].C(N=C=NCCCN(C)C)C.[NH2:66][NH2:67]>CN(C=O)C.O>[Cl:54][CH2:42][CH2:41][CH2:40][CH:36]([C:37]1[NH:67][N:66]=[C:25]([NH:24][C:14]2[CH:15]=[CH:16][C:17]([N:18]3[C:22]([CH3:23])=[N:21][CH:20]=[N:19]3)=[C:12]([F:11])[CH:13]=2)[N:26]=1)[C:33]1[CH:32]=[CH:31][C:30]([F:29])=[CH:35][CH:34]=1

Participants

9

Reactant 6

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 183545112-(4-Fluorophenyl)pent-4-enoic acidHCID 178504012HCID 178504012, compound

Product 1

HCID 668602155-(4-chloro-1-(4-fluorophenyl)butyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amineYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of N-ethyldiisopropylamine (1.29 mL, 7.39 mmol) in DMF (15 mL) was added to a 50 mL round bottom flask charged with a mixture of methyl 3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenylcarbamimidothioate hydroiodide (1.16 g, 2.96 mmol, from preparation Q), 2-(4-fluorophenyl)pent-4-enoic acid (0.750 g, 3.25 mmol, from preparation AC), 1-hydroxybenzotriazole hydrate (0.905 g, 5.91 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.133 g, 5.91 mmol). The resulting mixture was magnetically stirred under nitrogen for 18 h at rt. Hydrazine (0372 mL, 11.84 mmol) was added to the reaction solution and the mixture was heated at 70° C. for 2 hr. The crude reaction mixture was poured into water (250 mL) and extracted with ethyl acetate (2×150 mL). The organic layer was washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to afford 5-(4-chloro-1-(4-fluorophenyl)butyl)-N-(3-fluoro-4-(5-methyl-1H-1,2,4-triazol-1-yl)phenyl)-1H-1,2,4-triazol-3-amine (1.02 g, 2.298 mmol, 78% yield). LC-MS (M+H)+ 443.3, ˜50% purity by UV integration. Used crude isolate in the next step without purification.

Workup

  1. temperaturethe mixture was heated at 70° C. for 2 hr
  2. customThe crude reaction mixture
  3. extractionextracted with ethyl acetate (2×150 mL)
  4. washThe organic layer was washed with brine (50 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dbf88654bf9541f4b3411eadb943c7dd
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

Loading…