Toluene → methyl 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-ethylbenzoate

HRID 915586Notes

Reaction equation

HRID 915586 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:12][C:13]2[N:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[CH3:24])[N:16]=[C:15]([C:25]([CH3:28])([CH3:27])[CH3:26])[CH:14]=2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH2:29](B(O)O)[CH3:30].C(Cl)Cl.C1(C)C=CC=CC=1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[C:25]([C:15]1[CH:14]=[C:13]([NH:12][C:5]2[CH:4]=[CH:3][C:2]([CH2:29][CH3:30])=[CH:11][C:6]=2[C:7]([O:9][CH3:10])=[O:8])[N:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[CH3:24])[N:16]=1)([CH3:28])([CH3:27])[CH3:26]

Participants

7

Reactant 4

HCID 1140TolueneHCID 6344DichloromethaneHCID 521157Ethylboronic acidHCID 58958623methyl 5-bromo-2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoate

Product 1

HCID 58958598methyl 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-ethylbenzoateYield 61%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of methyl 5-bromo-2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoate (Example 234, 1.15 g, 4.13 mmol), ethylboronic acid (1.16 g, 15.7 mmol), and Pd(dppf)Cl2.CH2Cl2 (114 mg, 0.16 mmol) was added toluene (20 mL) and dioxane (5 mL). The resulting solution was degassed under nitrogen for 30 min, followed by addition of sodium bicarbonate (2 M aq solution, 15 mL). The mixture was then heated to 85° C. for 16 h. The reaction mixture was allowed to cool to rt. The solvent was removed under reduced pressure, and the residue was purified by silica gel flash chromatography using 0 to 10% ethyl acetate in hexanes to afford 606 mg (61%) of the title compound. 1H NMR (300 MHz, CD2Cl2) δ 9.17 (s, 1H), 7.68 (s, 1H), 7.22-7.33 (m, 6H), 6.08 (s, 1H), 3.70 (s, 3H), 2.51 (q, 2H), 2.05 (s, 3H), 1.30 (s, 9H), 1.14 (t, 3H). ES-MS m/z 392.2 (MH+); HPLC RT (min) 4.62.

Workup

  1. customThe resulting solution was degassed under nitrogen for 30 min
  2. additionfollowed by addition of sodium bicarbonate (2 M aq solution, 15 mL)
  3. temperatureto cool to rt
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-c32987e78db14c6d91d9166ea5590b2e
Source dataset
uspto-grants-2007_09
Patent number
US07265144B2

Reaction notes

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