Potassium Phosphate, Tribasic → 2-{(2-Methoxyethyl)[(trans-2-methylcyclopropyl)methyl]amino}-6-[methyl(methylsulfonyl)amino]isonicotinic acid

HRID 1944573Notes

Reaction equation

HRID 1944573 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N:11]([CH3:16])[S:12]([CH3:15])(=[O:14])=[O:13])[N:10]=1)[C:5]([OH:7])=[O:6].Cl.[CH3:18][O:19][CH2:20][CH2:21][NH:22][CH2:23][C@@H:24]1[CH2:26][C@H:25]1[CH3:27].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC(N(C)C)=O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:18][O:19][CH2:20][CH2:21][N:22]([CH2:23][C@@H:24]1[CH2:26][C@H:25]1[CH3:27])[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N:11]([CH3:16])[S:12]([CH3:15])(=[O:14])=[O:13])[N:10]=1)[C:5]([OH:7])=[O:6]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 167483252-Chloro-6-[methyl(methylsulfonyl)amino]isonicotinic acidHCID 86616985trans (2-Methoxyethyl)[(2-methylcyclopropyl)methyl]amine hydrochloride

Product 1

HCID 694982882-{(2-Methoxyethyl)[(trans-2-methylcyclopropyl)methyl]amino}-6-[methyl(methylsulfonyl)amino]isonicotinic acid

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of 2-chloro-6-[methyl(methylsulfonyl)amino]isonicotinic acid (20 g, 75.6 mmol), trans (2-methoxyethyl)[(2-methylcyclopropyl)methyl]amine hydrochloride (17.65 g, 98.2 mmol), potassium phosphate (48.12 g, 226.7 mmol) in DMA (300 mL) was degassed with argon for 10 min. Pd(PtBu3)2 (1.93 g, 3.78 mmol) was added and the reaction mixture was degassed with argon for 10 min. The reaction mixture was stirred at 110° C. for 24 hours. The reaction was cooled to rt, filtered through celite, rinsed with EtOAc, diluted with water, the pH was adjusted to 3-4 with 1N HCl, extracted with EtOAc (×3). The organic layer was washed with aq LiCl, dried over sodium sulfate and concentrated in vacuo to give 2-{(2-methoxyethyl)[(trans-2-methylcyclopropyl)methyl]amino}-6-[methyl(methylsulfonyl)amino]isonicotinic acid. 1H NMR (400 MHz, CDCl3) δ 7.05 (s, 1H), 7.62 (s, 1H), 3.76 (t, J=6.3 Hz, 2H), 3.60 (t, J=6.3 Hz, 2H), 3.52-3.43 (m, 1H), 3.39 (s, 3H), 3.36 (s, 3H), 3.38-3.30 (m, 1H), 3.18 (s, 3H), 1.23 (d, J=6.1 Hz, 3H), 0.82-0.64 (m, 2H), 0.46-0.39 (m, 1H), 0.32-0.25 (m, 1H).

Workup

  1. customwas degassed with argon for 10 min
  2. customthe reaction mixture was degassed with argon for 10 min
  3. temperatureThe reaction was cooled to rt
  4. filtrationfiltered through celite
  5. washrinsed with EtOAc
  6. additiondiluted with water
  7. extractionextracted with EtOAc (×3)
  8. washThe organic layer was washed with aq LiCl
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0451064183eb489cbd137ccbe32d1122
Source dataset
uspto-grants-2013_03
Patent number
US08394837B2

Reaction notes

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