Ammonium Hydroxide → HCID 68642173, compound

HRID 403521Notes

Reaction equation

HRID 403521 reaction equation
Br[C:2]1[C:3]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[N:4][N:5]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=1.[Cu][C:29]#[N:30].[OH-].[NH4+]>CN(C)C=O.C(OCC)(=O)C.O>[F:21][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=1[CH2:14][N:5]1[C:6]([C:7]2[CH:12]=[CH:11][C:10]([CH3:13])=[CH:9][CH:8]=2)=[C:2]([C:29]#[N:30])[C:3]([C:22]2[N:27]=[CH:26][CH:25]=[CH:24][N:23]=2)=[N:4]1

Participants

7

Reactant 3

HCID 14923Ammonium HydroxideHCID 66632350HCID 66632350, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 68642173HCID 68642173, compoundYield 90.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
23 °C

Procedure

To a suspension of 2-(4-bromo-1-(2-fluorobenzyl)-5-p-tolyl-1H-pyrazol-3-yl)pyrimidine (145 mg, 0.343 mmol) in N,N-dimethylformamide was added copper(I) cyanide (178 mg, 1.884 mmol). 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 45 min, and then further diluted with ethyl acetate (75 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The organics were combined and washed with brine (50 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-(pyrimidin-2-yl)-5-p-tolyl-1H-pyrazole-4-carbonitrile (114 mg, 0.309 mmol, 90% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.92 (d, 2H), 7.34-7.23 (m, 6H), 7.09-6.98 (m, 3H), 5.52 (s, 2H), 2.42 (s, 3H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (2×50 mL)
  3. washwashed with brine (50 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customto give the crude product as an oil
  8. customPurification by silica gel chromatography (hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-5624c7f3db1d4f38b5c718bf9bd81f2b
Source dataset
uspto-grants-2014_06
Patent number
US08748442B2

Reaction notes

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