Potassium Carbonate → benzyl 4-[4-[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]-5-pyridin-4-ylpyrazol-1-yl]piperidine-1-carboxylate

HRID 1726399Notes

Reaction equation

HRID 1726399 reaction equation
Br[C:2]1[C:3](C2C=CN=CC=2)=[N:4][N:5]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:14])[CH2:9][CH2:8]2)[CH:6]=1.[CH2:29]([O:36]/[N:37]=[C:38]1\[CH2:39][CH2:40][C:41]2[C:46]\1=[CH:45][CH:44]=[C:43](B(O)O)[CH:42]=2)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O>[CH2:29]([O:36]/[N:37]=[C:38]1\[CH2:39][CH2:40][C:41]2[C:46]\1=[CH:45][CH:44]=[C:43]([C:2]1[CH:3]=[N:4][N:5]([CH:7]3[CH2:8][CH2:9][N:10]([C:13]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)=[O:14])[CH2:11][CH2:12]3)[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1)[CH:42]=2)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 68923615benzyl 4-(4-bromo-3-(pyridin-4-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylateHCID 87623866[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]boronic acid

Product 1

HCID 87625891benzyl 4-[4-[(1E)-1-phenylmethoxyimino-2,3-dihydroinden-5-yl]-5-pyridin-4-ylpyrazol-1-yl]piperidine-1-carboxylateYield 166.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To benzyl 4-(4-bromo-3-(pyridin-4-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.32 g; Example 5, Step 1) in 10 mL acetonitrile and 3 mL water was added 0.315 g (E)-1-(benzyloxyimino)-2,3-dihydro-1H-inden-5-ylboronic acid (prepared as described in example 2, step 4) and 0.30 g potassium carbonate. The reaction mixture was purged with nitrogen and 84 mg tetrakis(triphenyphosphine)palladium(0) catalyst was added. The reaction mixture heated to 80° C. for 2 hours, filtered through celite, and the filter cake was washed with acetonitrile. The filtrate was evaporated under vacuum to yield crude product. The residue was purified by chromatography, eluting with ethyl acetate to afford 0.36 g (83% yield) product as a colorless oil. 1H NMR (CDCl3) was consistent with the desired structure. LC/MS showed one peak with a M+1 molecular ion of m/z 598.3 by positive ESI.

Workup

  1. customThe reaction mixture was purged with nitrogen and 84 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 under vacuum
  6. customto yield crude product
  7. customThe residue was purified by chromatography
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-0993941776bf4191adb782890b2a9cdc
Source dataset
uspto-grants-2009_02
Patent number
US07491829B2

Reaction notes

Loading…