Sodium Formate → 5-Isopropyl-N-{1-methyl-4-(4-methylphenyl)-3-[2-(2-pyrimidinyloxy)ethoxy]-1H-pyrazol-5-yl}-pyridine-2-sulfonamide

HRID 1062744Notes

Reaction equation

HRID 1062744 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([O:8][CH2:9][CH2:10][O:11][C:12]2[C:16]([C:17]3[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=3)=[C:15]([NH:24][S:25]([C:28]3[CH:33]=[CH:32][C:31]([CH:34]([CH3:36])[CH3:35])=[CH:30][N:29]=3)(=[O:27])=[O:26])[N:14]([CH3:37])[N:13]=2)=[N:6][CH:7]=1.C([O-])=O.[Na+].[C]=O>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C)C=O>[CH:34]([C:31]1[CH:32]=[CH:33][C:28]([S:25]([NH:24][C:15]2[N:14]([CH3:37])[N:13]=[C:12]([O:11][CH2:10][CH2:9][O:8][C:5]3[N:4]=[CH:3][CH:2]=[CH:7][N:6]=3)[C:16]=2[C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)(=[O:26])=[O:27])=[N:29][CH:30]=1)([CH3:36])[CH3:35]

Participants

6

Reactant 3

HCID 2723810Sodium FormateHCID 9829887N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamideHCID 178418416HCID 178418416, compound2×

Product 1

HCID 222818935-Isopropyl-N-{1-methyl-4-(4-methylphenyl)-3-[2-(2-pyrimidinyloxy)ethoxy]-1H-pyrazol-5-yl}-pyridine-2-sulfonamideYield 46.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
100 °C

Procedure

N-[3-{2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy}-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropylpyridine-2-sulfonamide (Example 41) (393 mg), powdered sodium formate (68 mg) and dichlorobis(triphenylphosphine)palladium (II) (9.4 mg) were placed in a Wheaton® vial (2.5 ml) volume containing a stirring vane. Dimethylformamide (2.0 ml) which had been saturated with carbon monoxide gas at room temperature, was added to the vial so as to produce a yellow solution. The sealed vial was magnetically stirred at 100° C. (oil bath temperature) for 3 hours before being left to cool to room temperature. A TLC check showed the presence of a significant amount of starting material. Addition of dichlorobis(triphenylphosphine)palladium (II) (9.4 mg) and resaturation of the dimethylformamide with carbon monoxide was followed by heating of the vial's contents for a further hour. On cooling to room temperature, the solution was degassed by bubbling nitrogen gas through it. The mixture was treated with ethyl acetate and filtered through a bed of Celite™ (5 g), followed by washing the Celite with ethyl acetate so as to take the solution volume to 100 ml. Washing of this phase with water (3×100 ml) and brine (100 ml), was followed by drying (Na2SO4), filtering and concentration in vacuo. This afforded the title compound as white crystals (157 mg).

Workup

  1. additioncontaining a stirring vane
  2. additionwas added to the vial so as
  3. customto produce a yellow solution
  4. waitbefore being left
  5. temperatureto cool to room temperature
  6. temperatureby heating of the vial's contents for a further hour
  7. temperatureOn cooling to room temperature
  8. customthe solution was degassed
  9. customby bubbling nitrogen gas through it
  10. additionThe mixture was treated with ethyl acetate
  11. filtrationfiltered through a bed of Celite™ (5 g)
  12. washby washing the Celite with ethyl acetate so as
  13. washWashing of this phase with water (3×100 ml) and brine (100 ml)
  14. dry with materialby drying (Na2SO4)
  15. filtrationfiltering
  16. concentrationconcentration in vacuo

Sources & evidence

ORD record
ord-4523f90dd2ae40169d1f01ce7ee61d00
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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