Sodium Carbonate → N,N-Diethyl-4-[[4-(4-fluorophenyl)-3,5-dimethylpyrazol-1-yl]-(3-methoxyphenyl)-methyl]-benzamide

HRID 1061855Notes

Reaction equation

HRID 1061855 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].[F:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C([O-])([O-])=O.[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCO.O>[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:35]3[CH:36]=[CH:37][C:32]([F:31])=[CH:33][CH:34]=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

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 22285739N,N-Diethyl-4-[(4-iodo-3,5-dimethyl-pyrazol-1-yl)-(3-methoxy-phenyl)-methyl]-benzamide

Product 1

HCID 22285746N,N-Diethyl-4-[[4-(4-fluorophenyl)-3,5-dimethylpyrazol-1-yl]-(3-methoxyphenyl)-methyl]-benzamideYield 88%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 19096565Water ethanolSolvent

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 (145 mg, 0.281 mmol) in 20 Ml EtOH/H2O (9:1) at room temperature was added 4-fluorobenzene boronic acid (118 mg, 0.842 mmol), Na2CO3 (90.0 mg, 0.842 mmol) and tetrakis(triphenylphosphine) palladium (0) (30.0 mg, 0.005 mmol). The mixture was cooled to −78° C., de-oxygenated under reduced pressure and purged with nitrogen gas. The mixture was refluxed for 2 hours, 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 30% ethyl acetate/hexanes, collecting 8 Ml fractions. The product containing fractions were collected and concentrated to give the desired product (120 mg, 88%) as a clear colorless solid. 300 MHz 1H NMR (CDCl3) δ 7.33 (d, J=8.3 Hz, 2H), 7.16-7.23 (m, 5H), 7.04-7.15 (m, 2H), 6.71-6.84 (m, 3H), 6.55 (s, 1H), 3.74 (s, 3H), 3.52 (br s, 2H), 3.27 (br s, 2H), 2.19 (s, 3H), 2.16 (s, 3H), 1.21 (br s, 3H), 1.09 (br s, 3H), MS (M+1) 486.2.

Workup

  1. custompurged with nitrogen gas
  2. temperatureThe mixture was refluxed for 2 hours
  3. temperaturecooled to room temperature
  4. filtrationfiltered through a Celite pad
  5. concentrationconcentrated
  6. customPurification of the crude material
  7. washeluting with 30% ethyl acetate/hexanes
  8. customcollecting 8 Ml fractions
  9. additionThe product containing fractions
  10. customwere collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c4689ea43bfe4e1ab229e4eb90565d62
Source dataset
uspto-grants-2005_11
Patent number
US06960609B2

Reaction notes

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