4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride → 4-(4-bromo-2-fluoroanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide

HRID 917751Notes

Reaction equation

HRID 917751 reaction equation
[NH2:1][O:2][CH2:3][CH2:4][OH:5].[Br:6][C:7]1[CH:24]=[CH:23][C:10]([NH:11][C:12]2[C:13]([C:20](O)=[O:21])=[CH:14][N:15]([CH3:19])[C:16](=[O:18])[CH:17]=2)=[C:9]([F:25])[CH:8]=1.C[N+]1(C2N=C(OC)N=C(OC)N=2)CCOCC1.[Cl-]>CO>[Br:6][C:7]1[CH:24]=[CH:23][C:10]([NH:11][C:12]2[C:13]([C:20]([NH:1][O:2][CH2:3][CH2:4][OH:5])=[O:21])=[CH:14][N:15]([CH3:19])[C:16](=[O:18])[CH:17]=2)=[C:9]([F:25])[CH:8]=1

Participants

5

Reactant 3

HCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 3014186Ethanol, 2-(aminooxy)-HCID 115809254-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid

Product 1

HCID 111887724-(4-bromo-2-fluoroanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamideYield 38%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-(Aminooxy)ethanol, 4-(4-bromo-2-fluoroanilino)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxylic acid and DMT-MM were reacted in MeOH as outlined in example 33, step D. Further purification by flash chromatography on silica gel (EtOAc followed by 10% MeOH/CH2Cl2) gave 4-(4-bromo-2-fluoroanilino)-N-(2-hydroxyethoxy)-1-methyl-6-oxo-1,6-dihydro-3-pyridinecarboxamide (38%); m.p. (EtOAc/Hexane) 124-128° C. 1H NMR [400 MHz, (CD3)2SO] δ 11.64 (br s, 1H), 9.50 (br s, 1H), 8.13 (s, 1H), 7.69-7.65 (m, 1H), 7.47-7.41 (m, 2H), 5.53 (d, J=0.7 Hz, 1H), 4.78 (s, 1H), 3.91 (t, J=5.0 Hz, 2H), 3.61 (t, J=5.0 Hz, 2H), 3.36 (s, 3H). LCMS (ACPI−) 400 (80%), 398 (100%). Anal. Calcd for C15H15BrFN3O4.0.25 H2O: C, 44.5; H, 3.9; N, 10.4. Found C, 44.3; H, 3.5; N, 10.2.

Workup

  1. customFurther purification by flash chromatography on silica gel (EtOAc followed by 10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-cfa3313bdfa649e4bda7c6819ca1942b
Source dataset
uspto-grants-2007_09
Patent number
US07273877B2

Reaction notes

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