Potassium Carbonate → 6-[4-[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]pyridine-3-carbonitrile

HRID 1726401Notes

Reaction equation

HRID 1726401 reaction equation
Br[C:2]1[C:3]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)=[N:4][N:5]([C:7]2[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=2)[CH:6]=1.[CH2:21]([O:28]/[N:29]=[C:30]1\[CH2:31][CH2:32][C:33]2[C:38]\1=[CH:37][CH:36]=[C:35](B(O)O)[CH:34]=2)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[CH2:21]([O:28]/[N:29]=[C:30]1\[CH2:31][CH2:32][C:33]2[C:38]\1=[CH:37][CH:36]=[C:35]([C:2]1[C:3]([C:15]3[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=3)=[N:4][N:5]([C:7]3[CH:14]=[CH:13][C:10]([C:11]#[N:12])=[CH:9][N:8]=3)[CH:6]=1)[CH:34]=2)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 689208226-(4-bromo-3-(pyridin-4-yl)-1H-pyrazol-1-yl)nicotinonitrileHCID 87623866[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]boronic acid

Product 1

HCID 876245286-[4-[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]-3-pyridin-4-ylpyrazol-1-yl]pyridine-3-carbonitrileYield 39%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To 6-(4-bromo-3-(pyridin-4-yl)-1H-pyrazol-1-yl)nicotinonitrile (0.26 g; Example 6, step 1) in 16 mL acetonitrile and 4 mL water was added (E)-1-(benzyloxyimino)-2,3-dihydro-1H-inden-5-ylboronic acid (0.34 g; Example 2, Step 4) and 0.33 g potassium carbonate. The reaction mixture was purged with nitrogen and 46 mg tetrakis(triphenyphosphine)palladium(0) catalyst was added. The reaction mixture was heated to 80° C. for 1.5 hours, filtered through celite, the filter cake was washed with acetonitrile. The filtrate was evaporated to yield crude product, which was purified by chromatography, eluting with a 10:1 mixture of dichloromethane-methanol to afford 0.15 g (36% yield) product as a pale yellow solid. 1H NMR (CDCl3) was consistent with the desired structure. LC/MS showed one peak with a M+1 molecular ion of m/z 483.2 by positive ESI.

Workup

  1. customThe reaction mixture was purged with nitrogen and 46 mg tetrakis(triphenyphosphine)palladium(0) catalyst
  2. additionwas added
  3. filtrationfiltered through celite
  4. washthe filter cake was washed with acetonitrile
  5. customThe filtrate was evaporated
  6. customto yield crude product, which
  7. customwas purified by chromatography
  8. washeluting with a 10:1 mixture of dichloromethane-methanol

Sources & evidence

ORD record
ord-7359aa0ca85b47fa9f4787c4b6133316
Source dataset
uspto-grants-2009_02
Patent number
US07491829B2

Reaction notes

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