Ammonium Chloride → HCID 56598120, compound

HRID 403522Notes

Reaction equation

HRID 403522 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:12]=[C:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[N:10]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[N:9]=2)=[N:6][CH:7]=1.[CH3:27][S:28]([O-:30])=[O:29].[Na+].[NH4+].[Cl-].C([O-])(O)=O.[Na+]>CS(C)=O.[Cu]I>[F:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH2:19][N:10]1[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:12][C:8]([C:5]2[CH:4]=[CH:3][C:2]([S:28]([CH3:27])(=[O:30])=[O:29])=[CH:7][N:6]=2)=[N:9]1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 2733271Sodium methanesulfinateHCID 56598922HCID 56598922, compound

Product 1

HCID 56598120HCID 56598120, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of 5-bromo-2-(1-(2-fluorobenzyl)-5-(pyridin-2-yl)-1H-pyrazol-3-yl)pyridine, copper(I) iodide (3.0 eq.) and sodium methanesulfinate (3.0 eq.) in DMSO was warmed to 130° C. and stirred at that temperature until completion (by LC/MS analysis). Once complete (reaction time was typically 3-6 h), the reaction solution was cooled to rt and saturated solutions of NH4Cl and NaHCO3 (2:1 ratio) were added. The resultant mixture was stirred for 1 h and then extracted with EtOAc. The organic phases were dried over Na2SO4, filtered and conc. The crude product was purified using SiO2 chromatography and an appropriate gradient (ethyl acetate/hexanes) to give 2-(1-(2-fluorobenzyl)-5-(pyridin-2-yl)-1H-pyrazol-3-yl)-5-(methylsulfonyl)pyridine as a white solid (61% yield). 1H NMR (400 MHz, CDCl3) δ 9.14 (br. s, 1H), 8.63 (d, 1H), 8.23 (m, 2H), 7.75 (app. td, 1H), 7.66 (d, 1H), 7.40 (s, 1H), 7.24 (m, 1H), 7.18 (m, 1H), 7.00 (m, 1H), 6.96 (m, 1H), 6.92 (m, 1H), 6.13 (s, 2H), 3.13 (s, 3H) ppm. MS: [M+H]=409.

Workup

  1. customOnce complete (reaction time
  2. temperature), the reaction solution was cooled to rt
  3. extractionextracted with EtOAc
  4. dry with materialThe organic phases were dried over Na2SO4
  5. filtrationfiltered
  6. customconc. The crude product was purified

Sources & evidence

ORD record
ord-e48ddf1d25ec455ab1f871caf5ede7e3
Source dataset
uspto-grants-2014_06
Patent number
US08748442B2

Reaction notes

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