4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → HCID 10150539, compound

HRID 1835653Notes

Reaction equation

HRID 1835653 reaction equation
[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([O:21][CH3:22])=[O:20])=[CH:15][C:14]=2[F:23])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=O.[NH2:24][O:25][CH2:26][CH2:27][OH:28].[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CO>[F:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:4]([C:5]([NH:24][O:25][CH2:26][CH2:27][OH:28])=[O:7])[C:3]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([O:21][CH3:22])=[O:20])=[CH:15][C:14]=1[F:23]

Participants

5

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride2×HCID 3014186Ethanol, 2-(aminooxy)-HCID 12135108HCID 12135108, compound

Product 1

HCID 10150539HCID 10150539, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

3,4-difluoro-2-[2-fluoro-4-(methoxycarbonyl)anilino]benzoic acid (320 mg, 0.99 mmol) was dissolved in MeOH (50 mL) to which was added 2-(aminooxy)ethanol followed by 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methymorpholinium chloride [DMT-MM, prepared according to the procedure of Kunishima et al [Tetrahedron, 55, 13159-13170 (1999)]] (326 mg, 1.18 mmol), This mixture was stirred 15 h. at room temperature. The MeOH was removed under reduced pressure and the resulting oil dissolved in EtOAc (100 mL), which was washed with water (2×100 mL), brine (100 mL) and dried (Na2SO4). The solvent was removed under reduced pressure to afford a crude yellow oil which was purified by filtration through a plug of silica gel (100% EtOAc as eluant) to give methyl 4-(2,3-difluoro-6-{[(2-hydroxyethoxy)amino]carbonyl} anilino)-3-fluorobenzoate as a cream solid (79%); m.p. (EtOAc/hexane) 162-165° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.82 (v br s, 1 H), 9.08 (v br s, 1 H), 7.70-7.62 (m, 2 H), 7.49-7.43 (m, 1 H), 7.38-7.29 (m, 1 H), 6.81 (ddd, J=8.6, 8.6, 4.7 Hz, 1 H), 4.76 (v br s, 1 H), 3.83-3.78 (m, 5 H), 3.53 (t, J=4.8 Hz, 2 H). Anal. calcd. for C17H15F3N2O5: C, 53.1; H, 3.9; N, 7.3. Found C, 53.3; H, 4.2; N, 7.3.

Workup

  1. customprepared
  2. customThe MeOH was removed under reduced pressure
  3. dissolutionthe resulting oil dissolved in EtOAc (100 mL)
  4. washwhich was washed with water (2×100 mL), brine (100 mL)
  5. dry with materialdried (Na2SO4)
  6. customThe solvent was removed under reduced pressure
  7. customto afford a crude yellow oil which
  8. filtrationwas purified by filtration through a plug of silica gel (100% EtOAc as eluant)

Sources & evidence

ORD record
ord-de8279a4de854ab391896233a4165165
Source dataset
uspto-grants-2004_08
Patent number
US06770778B2

Reaction notes

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