2,6-Lutidine → N-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-4-methyl-3-(4-pyridin-3-yl-[1,2,3]triazol-1-yl)-benzamide

HRID 2109174Notes

Reaction equation

HRID 2109174 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[N:11]1[CH:15]=[C:14]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[N:13]=[N:12]1.C(Cl)(=O)C(Cl)=O.[NH2:28][C:29]1[C:30]([O:44][CH3:45])=[C:31]([NH:39][S:40]([CH3:43])(=[O:42])=[O:41])[CH:32]=[C:33]([C:35]([CH3:38])([CH3:37])[CH3:36])[CH:34]=1.N1C(C)=CC=CC=1C>C(Cl)Cl.CN(C=O)C.C1COCC1>[C:35]([C:33]1[CH:32]=[C:31]([NH:39][S:40]([CH3:43])(=[O:42])=[O:41])[C:30]([O:44][CH3:45])=[C:29]([NH:28][C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([N:11]3[CH:15]=[C:14]([C:16]4[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=4)[N:13]=[N:12]3)[CH:4]=2)[CH:34]=1)([CH3:38])([CH3:36])[CH3:37]

Participants

8

Reactant 4

HCID 79372,6-LutidineHCID 65578Oxalyl chlorideHCID 10214710N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methanesulfonamideHCID 210973314-Methyl-3-(4-pyridin-3-yl-1,2,3-triazol-1-yl)-benzoic acid

Product 1

HCID 21097217N-(5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-4-methyl-3-(4-pyridin-3-yl-[1,2,3]triazol-1-yl)-benzamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

4-Methyl-3-(4-pyridin-3-yl-1,2,3-triazol-1-yl)-benzoic acid (76.3 mg; 0.272 mmol) was suspended in 5 mL of CH2Cl2, and 1 mL of THF, and 0.04 mL (0.4 mmol) of oxalyl chloride was added. One drop of DMF was then added to the stirring suspension, and the mixture was stirred for 2 h. The resulting cloudy solution was concentrated to dryness and suspended in CH2Cl2. N-(3-Amino-5-tert-butyl-2-methoxy-phenyl)-methane-sulfonamide (81 mg; 0.30 mmol) was added, then 0.06 mL (0.5 mmol) of 2,6-lutidine, and the resulting solution was stirred overnight. The mixture was then washed with 1M NaHSO4, saturated NaHCO3, and brine. The organic portion was dried with Na2SO4, filtered, and concentrated. Chromatography (0-6.5% MeOH in CH2Cl2), with careful selection of only the pure fractions, provided 80 mg (0.15 mmol; 55%) of Example 14. ESI MS m/z 535 [C27H30N6O4S+H]+.

Workup

  1. concentrationThe resulting cloudy solution was concentrated to dryness
  2. washThe mixture was then washed with 1M NaHSO4, saturated NaHCO3, and brine
  3. dry with materialThe organic portion was dried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customChromatography (0-6.5% MeOH in CH2Cl2), with careful selection of only the pure fractions, provided 80 mg (0.15 mmol; 55%) of Example 14

Sources & evidence

ORD record
ord-fd0af20833874a808635d89f9ff130f5
Source dataset
uspto-grants-2009_04
Patent number
US07514458B2

Reaction notes

Loading…