Sodium Carbonate → N,N-Diethyl-4-[[4-(4-formyl-phenyl)-3,5-dimethyl-pyrazol-1-yl]-(3-methoxy-phenyl)-methyl]-benzamide

HRID 1061857Notes

Reaction equation

HRID 1061857 reaction equation
[CH2:1]([N:3]([CH2:29][CH3:30])[C:4](=[O:28])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([N:20]2[C:24]([CH3:25])=[C:23](I)[C:22]([CH3:27])=[N:21]2)[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)=[CH:7][CH:6]=1)[CH3:2].[C:31]([C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1)(O)=[O:32].C(=O)([O-])[O-].[Na+].[Na+]>CCO>[CH2:1]([N:3]([CH2:29][CH3:30])[C:4](=[O:28])[C:5]1[CH:10]=[CH:9][C:8]([CH:11]([N:20]2[C:24]([CH3:25])=[C:23]([C:37]3[CH:38]=[CH:39][C:34]([CH:31]=[O:32])=[CH:35][CH:36]=3)[C:22]([CH3:27])=[N:21]2)[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)=[CH:7][CH:6]=1)[CH3:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 3121834-Carboxyphenylboronic AcidHCID 22285739N,N-Diethyl-4-[(4-iodo-3,5-dimethyl-pyrazol-1-yl)-(3-methoxy-phenyl)-methyl]-benzamide

Product 1

HCID 22285742N,N-Diethyl-4-[[4-(4-formyl-phenyl)-3,5-dimethyl-pyrazol-1-yl]-(3-methoxy-phenyl)-methyl]-benzamideYield 93%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
-78 °C

Procedure

To a stirring solution of N,N-Diethyl-4-[(4-iodo-3,5-dimethyl-pyrazol-1-yl)-(3-methoxy-phenyl)-methyl]-benzamide (300 mg, 0.58 mmol) in 40 mL EtOH/H20 (9:1) at room temperature was added 4-carboxybenzeneboronic acid (261 mg, 1.74 mmol), sodium carbonate (184 mg, 1.74 mmol) and tetrakistriphenylphosphine palladium (0) (200 mg, 0.174 mmol). The mixture was cooled to −78° C., de-oxygenated under reduced pressure and purged with nitrogen gas. The mixture was refluxed for 3 h, cooled to room temperature, filtered through a Celite pad and concentrated under reduce pressure. Purification of the crude material was accomplished by flash chromatography on a 2×15 cm column, eluting with 50% ethyl acetate/hexanes, collecting 8 mL fractions. The product containing fractions were collected and concentrated to give the desired product (267 mg, 93%) as a clear colorless solid. 300 MHz 1H NMR (CDCl3) δ 10.1 (s, 1H), 7.90 (d, J=8.3 Hz, 2H), 7.21-7.42 (m, 7H), 6.78-6.86 (m, 3H), 6.57 (s, 1H), 3.75 (s, 3H), 3.52 (brs, 2H), 3.27 (brs, 2H), 2.26 (s, 6H), 1.24 (brs, 3H), 1.22 (brs, 3H); MS (M+1) 496.2.

Workup

  1. custompurged with nitrogen gas
  2. temperatureThe mixture was refluxed for 3 h
  3. temperaturecooled to room temperature
  4. filtrationfiltered through a Celite pad
  5. concentrationconcentrated
  6. customPurification of the crude material
  7. washeluting with 50% ethyl acetate/hexanes
  8. customcollecting 8 mL fractions
  9. additionThe product containing fractions
  10. customwere collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-19fa6839fbc94f87840e6e4ea2a0f236
Source dataset
uspto-grants-2005_11
Patent number
US06960609B2

Reaction notes

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