Formic Acid → HCID 58970772, compound

HRID 1163080Notes

Reaction equation

HRID 1163080 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH:11][C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:13]=2[NH2:19])=[CH:6][CH:5]=1.[CH:21](O)=O>COC(OC)OC>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:5]=[CH:6][C:7]([CH2:10][N:11]2[C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:13]=3[N:19]=[CH:21]2)=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 284Formic AcidHCID 68428155HCID 68428155, compound

Product 1

HCID 58970772HCID 58970772, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 9005Trimethyl orthoformateSolvent

Procedure

A stirred solution 4-[(4-methyl-2-nitrophenylamino)methyl]benzoic acid methyl ester (7.0 g, 23 mmol,) in CH3OH was treated with 5% Pd/C (50% wet, 30% w/w) and hydrazine hydrate (5.8 g, 116 mmol). The reaction mixture was heated to reflux temperature for 2 h, cooled to room temperature and filtered through celite. The filtrate was evaporated to give a residue. The residue was dissolved in CH2Cl2, washed with water, dried over anhydrous Na2SO4 and evaporated to afford 4-[(2-amino-4-methylphenylamino)methyl]benzoic acid methyl ester, which was used in the next step without further purification. Yield: 93%. 1H NMR (400 MHz, CDCl3) 8.0 (d, J=8 Hz, 2H); 7.70 (d, J=8 Hz, 2H); 6.60 (m, 2H); 6.49 (d, 1H); 4.3 (s, 2H); 3.90 (d, 3H); 2.21 (s, 3H). LCMS (ESI+) 271 (MH+). A stirred solution of crude 4-[(2-amino-4-methylphenylamino)methyl]benzoic acid methyl ester (6 g, 22 mmol) in trimethylorthoformate was treated with formic acid (1.0 g), refluxed for 2 h, cooled to room temperature and evaporated under reduced pressure. The resultant residue was purified by column chromatography using 1% MeOH/CHCl3 to afford 4-[(5-methylbenzimidazol-1-yl)methyl]benzoic acid methyl ester Yield: 61%. 1H NMR (400 MHz, CDCl3): 8.0 (d, J=8 Hz, 1H); 7.93 (s, 1H); 7.62 (s, 1H); 7.26 (s, 1H); 7.21 (d, J=8 Hz, 2H); 7.08 (m, 2H); 5.39 (s, 2H); 3.90 (s, 3H); 2.47 (s, 3H). LCMS (ESI+) 281 (MH+).

Workup

  1. customwas used in the next step without further purification
  2. temperaturerefluxed for 2 h
  3. customevaporated under reduced pressure
  4. customThe resultant residue was purified by column chromatography

Sources & evidence

ORD record
ord-f74b8bdf85f9481c87365d8513d61b34
Source dataset
uspto-grants-2010_10
Patent number
US07820825B2

Reaction notes

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