Pyridine → Methyl 2-chloro-6-[methyl(pyridin-3-ylsulfonyl)amino]isonicotinate

HRID 1944578Notes

Reaction equation

HRID 1944578 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([NH:12][CH3:13])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6].N1C=CC=CC=1.Cl.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([S:27](Cl)(=[O:29])=[O:28])[CH:22]=1.CN(C1C=CC=CN=1)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([N:12]([CH3:13])[S:27]([C:23]2[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=2)(=[O:29])=[O:28])[N:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

6

Reactant 4

HCID 1049PyridineHCID 218852-DimethylaminopyridineHCID 12571517Pyridine-3-sulfonyl chloride hydrochlorideHCID 59028392Methyl 2-chloro-6-(methylamino)isonicotinate

Product 1

HCID 86616988Methyl 2-chloro-6-[methyl(pyridin-3-ylsulfonyl)amino]isonicotinateYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 2-chloro-6-(methylamino)isonicotinate (2.00 g, 9.97 mmol) in 3:1 CH2Cl2:pyridine (100 mL total) was added 3-pyridine sulfonyl chloride hydrochloride (6.40 g, 29.9 mmol) and dimethylaminopyridine (0.609 g, 4.98 mmol). Reaction heated to reflux at 50° C. After 36 h, reaction cooled to rt. Reaction diluted with CH2Cl2 (200 mL) and washed with 1N HCl (150 mL) solution. The aqueous solution was extracted with CH2Cl2 (100 mL×2). The combined organics were washed with brine (100 mL), dried over Mg2SO4, filtered, and concentrated in vacuo. Purification by normal-phase chromatography (20->40% EtOAc/hexanes) yielded 3.12 g (92%) of methyl 2-chloro-6-[methyl(pyridin-3-ylsulfonyl)amino]isonicotinate as a yellow residue. 1H NMR (CDCl3, 400 MHz) 8.95 (d, J=0.64 Hz, 1H); 8.82 (m, 1H); 8.03 (m, 2H); 7.67 (m, 1H); 7.45 (m, 1H); 3.99 (s, 3H); 3.39 (s, 3H); LC/MS [M+H]+=341.9.

Workup

  1. customReaction
  2. temperatureheated
  3. customreaction
  4. temperaturecooled to rt
  5. customReaction
  6. washwashed with 1N HCl (150 mL) solution
  7. extractionThe aqueous solution was extracted with CH2Cl2 (100 mL×2)
  8. washThe combined organics were washed with brine (100 mL)
  9. dry with materialdried over Mg2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification by normal-phase chromatography (20->40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-4a56ab030553405fa3dd1e7a8bb02962
Source dataset
uspto-grants-2013_03
Patent number
US08394837B2

Reaction notes

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