Methanesulfonamide → 5-chloro-4-[(5-chloro-6-cyclopropylpyridin-3-yl)oxy]-2-fluoro-N-(methanesulfonyl)benzamide

HRID 2048019Notes

Reaction equation

HRID 2048019 reaction equation
[Cl:1][C:2]1[C:3]([O:12][C:13]2[CH:14]=[N:15][C:16]([CH:20]3[CH2:22][CH2:21]3)=[C:17]([Cl:19])[CH:18]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7](O)=[O:8].[CH3:23][S:24]([NH2:27])(=[O:26])=[O:25].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([O:12][C:13]2[CH:14]=[N:15][C:16]([CH:20]3[CH2:22][CH2:21]3)=[C:17]([Cl:19])[CH:18]=2)=[CH:4][C:5]([F:11])=[C:6]([CH:10]=1)[C:7]([NH:27][S:24]([CH3:23])(=[O:26])=[O:25])=[O:8]

Participants

6

Reactant 3

HCID 72879MethanesulfonamideHCID 111923Propylphosphonic anhydrideHCID 58042402HCID 58042402, compound

Product 1

HCID 547677565-chloro-4-[(5-chloro-6-cyclopropylpyridin-3-yl)oxy]-2-fluoro-N-(methanesulfonyl)benzamideYield 83.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
72.5 °C

Procedure

The compound of Example 21 was also prepared according to the following method. To a solution of 5-chloro-4-[(5-chloro-6-cyclopropylpyridin-3-yl)oxy]-2-fluorobenzoic acid (Preparation 265, 45.0 g, 131.52 mmol) in tetrahydrofuran (180 mL) at room temperature was added methansulphonamide (25.02 g, 263.04 mmol), N-ethyl-N-diisopropylpropan-2-amine (68.81 mL, 394.56 mmol) and 1-propanephosphonic acid cyclic anhydride (167.36 g, 263.04 mmol as a 50% solution in ethyl acetate) and the mixture stirred and heated at 70-75° C. for 16 hours. The reaction mixture was concentrated under reduced pressure at 45° C. and water added (450 mL), the resulting slurry was stirred for 30 minutes, filtered and dried. The crude product was dissolved in 2-propanol (1285 mL) at 85° C. and cooled slowly over 16 hours. The resulting slurry was filtered, washed with 2-propanol (2×40 mL) and dried to give the title compound as an off-white solid (46 g, 83%).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure at 45° C.
  2. additionwater added (450 mL)
  3. stirringthe resulting slurry was stirred for 30 minutes
  4. filtrationfiltered
  5. customdried
  6. dissolutionThe crude product was dissolved in 2-propanol (1285 mL) at 85° C.
  7. temperaturecooled slowly over 16 hours
  8. filtrationThe resulting slurry was filtered
  9. washwashed with 2-propanol (2×40 mL)
  10. customdried

Sources & evidence

ORD record
ord-c6c6db2166c64989ada7c54658eccd90
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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