Stannous Chloride → 3-(5-amino-4-benzoyl-pyrazol-1-yl)-N-methoxy-4-methyl-benzamide

HRID 251331Notes

Reaction equation

HRID 251331 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=1[CH3:13])[C:5]([NH:7][O:8][CH3:9])=[O:6].N([O-])=O.[Na+].[Sn](Cl)Cl.[C:21]([C:29](=[CH:32][NH:33]C1C=CC=CC=1)[C:30]#[N:31])(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>O.Cl.CCOC(C)=O>[NH2:33][C:32]1[N:1]([C:2]2[CH:3]=[C:4]([CH:10]=[CH:11][C:12]=2[CH3:13])[C:5]([NH:7][O:8][CH3:9])=[O:6])[N:31]=[CH:30][C:29]=1[C:21](=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 4

HCID 24479Stannous ChlorideHCID 207670003-Amino-N-methoxy-4-methylbenzamideHCID 23668193Sodium NitriteHCID 67024306beta-Oxo-alpha-[(phenylamino)methylene]benzenepropanenitrile

Product 1

HCID 112334033-(5-amino-4-benzoyl-pyrazol-1-yl)-N-methoxy-4-methyl-benzamideYield 28%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 3-amino-N-methoxy-4-methyl-benzamide 1 (104 mg, 0.58 mmol) in water (2 ml) at 0° C. was added conc. HCl (2 mL) followed by the addition of sodium nitrite (44 mg, 0.63 mmol). The reaction mixture was stirred at 0° C. for 40 minutes then a solution of tin(II)chloride (245 mg, 1.30 mmol) in conc. HCl (1 mL) was added and the mixture was stirred for 40 minutes then allowed to stand at −20° C. for 20 hours before it was warmed to RT and concentrated to a white solid. The solid was triturated with ethanol, the solids were removed, and 2-benzoyl-3-phenylamino-acrylonitrile 5 (144 mg, 0.58 mmol, preparation: Grothaus, J. Am. Chem. Soc. 58, 1334 (1936)) was added and the mixture heated (bath T=65-70° C.) for 16 hr. The mixture was cooled to RT, concentrated and purified by flash chromatography, eluting with 1:1 EtOAc/hexanes to remove impurities then 100% EtOAc to give 3-(5-amino-4-benzoyl-pyrazol-1-yl)-N-methoxy-4-methyl-benzamide 6 as an off-white solid (41 mg, 0.12 mmol, 28%). HPLC (4 minute gradient) tR 1.93 min; MS m/z 351.1 [M+H]+; 1H NMR (DMSO-d6, 300 MHz) δ 11.88 (s 1 H, NH), 7.803 (m, 4 H), 7.56 (m, 4 H), 7.01 (s, 2 H, NH2), 3.32 (s, 3 H), 2.162 (s, 3 H) ppm;

Workup

  1. stirringthe mixture was stirred for 40 minutes
  2. waitto stand at −20° C. for 20 hours before it
  3. temperaturewas warmed to RT
  4. concentrationconcentrated to a white solid
  5. customThe solid was triturated with ethanol
  6. customthe solids were removed
  7. temperaturethe mixture heated (bath T=65-70° C.) for 16 hr
  8. temperatureThe mixture was cooled to RT
  9. concentrationconcentrated
  10. custompurified by flash chromatography
  11. washeluting with 1:1 EtOAc/hexanes
  12. customto remove impurities

Sources & evidence

ORD record
ord-526c74f307db4f54a42d995b7cfdcde5
Source dataset
uspto-grants-2011_01
Patent number
US07863314B2

Reaction notes

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