Ammonium Hydroxide → HCID 56598121, compound

HRID 403520Notes

Reaction equation

HRID 403520 reaction equation
Br[C:2]1[C:3]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[N:4][N:5]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[F:20])[C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[Cu][C:28]#[N:29].[OH-].[NH4+]>CN(C)C=O.C(OCC)(=O)C.O>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][N:5]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)=[C:2]([C:28]#[N:29])[C:3]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[N:4]1

Participants

7

Reactant 3

HCID 14923Ammonium HydroxideHCID 66633770HCID 66633770, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 56598121HCID 56598121, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
150 °C

Procedure

To a suspension of 2,2′-(4-bromo-1-(2-fluorobenzyl)-1H-pyrazole-3,5-diyl)dipyridine (200 mg, 0.489 mmol) in N,N-dimethylformamide (3.4 mL) was added copper (I) cyanide (253 mg, 2.69 mmol). The suspension was stirred at 150° C. for 2 h, at which point LC/MS indicated a complete reaction. The solution was cooled to 23° C. and 5 mL of water, 5 mL of ammonium hydroxide, and 5 mL of ethyl acetate were added. The blue heterogeneous mixture was stirred rapidly for 40 min, and then further diluted with ethyl acetate (150 mL) and water (75 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×75 mL). The organics were combined and washed with water (75 mL) and brine (75 mL), dried over magnesium sulfate, filtered, and the solvent was removed in vacuo to give the crude product as an oil. Purification by silica gel chromatography (hexanes/ethyl acetate) gave 1-(2-fluorobenzyl)-3,5-di(pyridin-2-yl)-1H-pyrazole-4-carbonitrile (161 mg, 0.453 mmol, 93% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.77-8.73 (m, 2H), 8.05-8.03 (m, 1H), 7.96-7.94 (m, 1H), 7.87 (dt, 1H), 7.78 (dt, 1H), 7.40-7.36 (m, 1H), 7.33-7.30 (m, 1H), 7.23-7.17 (m, 1H), 7.07-6.94 (m, 3H), 5.97 (s, 2H).

Workup

  1. customa complete reaction
  2. temperatureThe solution was cooled to 23° C.
  3. stirringThe blue heterogeneous mixture was stirred rapidly for 40 min
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (2×75 mL)
  6. washwashed with water (75 mL) and brine (75 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customthe solvent was removed in vacuo
  10. customto give the crude product as an oil
  11. customPurification by silica gel chromatography (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-7aee25943ad14e3090cf9b198e2b7351
Source dataset
uspto-grants-2014_06
Patent number
US08748442B2

Reaction notes

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