Sodium hydride → HCID 18519897, compound

HRID 1368595Notes

Reaction equation

HRID 1368595 reaction equation
[OH:1][CH2:2][CH2:3][O:4][C:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)=[C:8]([NH:17][S:18]([C:21]2[CH:26]=[CH:25][C:24]([CH:27]([CH3:29])[CH3:28])=[CH:23][N:22]=2)(=[O:20])=[O:19])[N:7]([CH3:30])[N:6]=1.[H-].[Na+].Cl[C:34]1[N:39]=[CH:38][C:37](S(C)(=O)=O)=[CH:36][N:35]=1>C1COCC1.CC(N(C)C)=O>[CH:27]([C:24]1[CH:25]=[CH:26][C:21]([S:18]([NH:17][C:8]2[N:7]([CH3:30])[N:6]=[C:5]([O:4][CH2:3][CH2:2][O:1][C:34]3[N:35]=[C:36]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:37]=[CH:38][N:39]=3)[C:9]=2[C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[CH:12][CH:11]=2)(=[O:19])=[O:20])=[N:22][CH:23]=1)([CH3:28])[CH3:29]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 156534822-Chloro-5-methanesulfonylpyrimidineHCID 22282040N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide

Product 1

HCID 18519897HCID 18519897, compoundYield 40.6%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of N-[3-(2-hydroxyethoxy)-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-yl]-5-isopropyl-2-pyridinesulfonamide (Example 40) (112 mg) in anhydrous THF (5 ml) at 0° C. and under an atmosphere of nitrogen was added sodium hydride (60% dispersion in oil, 21.8 mg) and the mixture was stirred for 5 minutes. To the mixture was added 2-chloro-5-(methylsulfonyl)pyrimidine (50 mg) in dimethylacetamide (1 ml). After stirring for 150 min. the reaction mixture was partitioned between ethyl acetate (50 ml) and saturated ammonium chloride solution (50 ml). The ethyl acetate layer was washed with brine (50 ml), dried (MgSO4), filtered and evaporated to dryness. Purification of the residue on a Phenomenex Magellen™ column using a 0.1M NH4OAc:MeCN gradient (95:5 to 60:40) over 5min. and then an isocratic flow (60:40) for 15 minutes gave the title compound as a white solid (31 mg).

Workup

  1. stirringAfter stirring for 150 min. the reaction mixture
  2. customwas partitioned between ethyl acetate (50 ml) and saturated ammonium chloride solution (50 ml)
  3. washThe ethyl acetate layer was washed with brine (50 ml)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customPurification of the residue on a Phenomenex Magellen™ column
  8. waitMeCN gradient (95:5 to 60:40) over 5min.

Sources & evidence

ORD record
ord-4257ddf94e864cc9aa5c9b3512bb7d33
Source dataset
uspto-grants-2003_06
Patent number
US06573270B1

Reaction notes

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