1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 1-Ethyl-2-{[2-(3-fluorophenyl)-pyrazol-3-yl]methyl}-5-cyano-1H-benzimidazole

HRID 1988700Notes

Reaction equation

HRID 1988700 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[NH:10][CH2:11][CH3:12])[C:5]#[N:6].[F:13][C:14]1[CH:15]=[C:16]([N:20]2[C:24]([CH2:25][C:26](O)=O)=[CH:23][CH:22]=[N:21]2)[CH:17]=[CH:18][CH:19]=1.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1>[CH2:11]([N:10]1[C:9]2[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=2[N:1]=[C:26]1[CH2:25][C:24]1[N:20]([C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([F:13])[CH:15]=2)[N:21]=[CH:22][CH:23]=1)[CH3:12]

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 38462923-Amino-4-(ethylamino)benzonitrileHCID 223799441-(3-Fluorophenyl)-5-carboxymethylpyrazole

Product 1

HCID 99027501-Ethyl-2-{[2-(3-fluorophenyl)-pyrazol-3-yl]methyl}-5-cyano-1H-benzimidazole

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a stirring solution of 3-amino-4-ethylaminobenzonitrile (887 mg, 5.5 mmol) and 1-(3-Fluorophenyl)-5-carboxymethylpyrazole (1.10 g, 5 mmol) in pyridine (5 mL) is added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.15 g, 6 mmol). The mixture is stirred at room temperature for 17.5 h, then concentrated. The residue is cooled in an ice bath, aqueous HCl is added with stirring, the precipitate is collected by filtration, rinsed well with water and dried. The solid is added to acetic acid (75 mL) and heated at reflux for 5.5 h. The mixture is cooled, concentrated, and purified by silica gel chromatography to give 1-Ethyl-2-{[2-(3-fluorophenyl)-pyrazol-3-yl]methyl}-5-cyano-1H-benzimidazole. The product is converted to the mesylate salt in acetone. 1H NMR (CDCl3): δ 8.17 (s, 1H), 7.89 (d, J=8.52 Hz, 1H), 7.68-7.75 (m 1H), 7.44-7.54 (m, 2H), 7.37-7.40 (m, 1H), 7.21-7.28 (m, 1H), 6.35 (d, J=1.65 Hz, 1H), 4.65 (s, 2H), 4.29 (q, J=7.14 Hz, 2H), 2.34 (s, 3H), 1.19 (t, J=7.14 Hz, 3H). LCMS 346.0 (MH+), 344.4 (MH−).

Workup

  1. concentrationconcentrated
  2. temperatureThe residue is cooled in an ice bath
  3. additionaqueous HCl is added
  4. stirringwith stirring
  5. filtrationthe precipitate is collected by filtration
  6. washrinsed well with water
  7. customdried
  8. additionThe solid is added to acetic acid (75 mL)
  9. temperatureheated
  10. temperatureat reflux for 5.5 h
  11. temperatureThe mixture is cooled
  12. concentrationconcentrated
  13. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-63b2182480b54a36aaab23ecc20829bc
Source dataset
uspto-grants-2010_01
Patent number
US07642267B2

Reaction notes

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