3-Aminobenzamide → 2-(3-Carbamoylphenylamino)-2-(4-fluoro-3-methoxyphenyl)acetic acid

HRID 1515505Notes

Reaction equation

HRID 1515505 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([NH2:7])=[O:6].[CH3:11][O:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][C:18]=1[F:19].O.[C:24]([OH:28])(=[O:27])[CH:25]=O>C(#N)C.CN(C=O)C>[C:5]([C:4]1[CH:3]=[C:2]([NH:1][CH:25]([C:15]2[CH:16]=[CH:17][C:18]([F:19])=[C:13]([O:12][CH3:11])[CH:14]=2)[C:24]([OH:28])=[O:27])[CH:10]=[CH:9][CH:8]=1)(=[O:6])[NH2:7]

Participants

6

Reactant 3

HCID 16453-AminobenzamideHCID 15620607Glyoxylic acid, monohydrateHCID 44558185(4-Fluoro-3-methoxyphenyl)boronic acid

Product 1

HCID 594794112-(3-Carbamoylphenylamino)-2-(4-fluoro-3-methoxyphenyl)acetic acidYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of 3-aminobenzamide (136 mg, 1.0 mmol), 7C (170 mg, 1.0 mmol) and glyoxylic acid monohydrate (92 mg, 1.0 mmol) in acetonitrile (5.0 mL) and DMF (1.2 mL) was heated at 55° C. for 2.0 h and then stirred at rt for 18 h. After removal of solvent, the crude was purified by silica gel column chromatography eluting with gradient methanol in methylene chloride to give 7D as a solid (190 mg, 60% yield). 1H NMR (400 MHz, Methanol-d4) δ ppm 3.85 (s, 3H) 5.11 (s, 1H) 6.79 (d, J=7.03 Hz, 1H) 7.04-7.15 (m, 5H) 7.27 (dd, J=8.35, 1.76 Hz, 1H); LC-MS 319 (M+H).

Workup

  1. customAfter removal of solvent
  2. customthe crude was purified by silica gel column chromatography
  3. washeluting with gradient methanol in methylene chloride

Sources & evidence

ORD record
ord-1a0e8761e7fd415b9cf336030774b11c
Source dataset
uspto-grants-2012_07
Patent number
US08222453B2

Reaction notes

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