Tris(1,1-dimethylethyl)phosphine → methyl 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-4-ethylbenzoate

HRID 915589Notes

Reaction equation

HRID 915589 reaction equation
[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]2[CH:20]=[C:19](Cl)[CH:18]=[CH:17][C:12]=2[C:13]([O:15][CH3:16])=[O:14])[N:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH3:28])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:29](B(O)O)[CH3:30].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[F-].[K+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]2[CH:20]=[C:19]([CH2:29][CH3:30])[CH:18]=[CH:17][C:12]=2[C:13]([O:15][CH3:16])=[O:14])[N:7]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH3:28])[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 521157Ethylboronic acidHCID 522689Potassium FluorideHCID 58958608methyl 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-4-chlorobenzoate

Product 1

HCID 58958599methyl 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-4-ethylbenzoateYield 81%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of methyl 2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-4-chlorobenzoate (Example 242, 50 mg, 0.13 mmol), ethylboronic acid (18.56 mg, 0.26 mmol), Pd2(dba)3 (5.8 mg, 0.006 mmol), tris(tert-butyl)phosphine (2.54 mg, 0.013 mmol), and potassium fluoride (14.6 mg, 0.25 mmol) was added dioxane (1 mL). The resulting solution was degassed under argon for 30 min and then heated to 110° C. for 16 h. The reaction mixture was then cooled to rt. The residue was diluted with ethyl acetate and filtered through a silica gel plug. The solvent was removed under reduced pressure, and the crude product was purified by HPLC purification using gradient elution from 30 to 100% acetonitrile in water to afford 39.8 mg (81%) of the title compound. 1H NMR (300 MHz, CD2Cl2) δ 9.23 (s, 1H), 7.74 (d, 1H), 7.23-7.29 (m, 4H), 7.03 (s, 1H), 6.57 (d, 1H), 6.09 (s, 1H), 3.69 (s, 3H), 2.55 (q, 2H), 2.06 (s, 3H), 1.30 (s, 9H), 1.15 (t, 3H). ES-MS m/z 392.2 (MH+); HPLC RT (min) 4.65.

Workup

  1. customThe resulting solution was degassed under argon for 30 min
  2. temperatureThe reaction mixture was then cooled to rt
  3. additionThe residue was diluted with ethyl acetate
  4. filtrationfiltered through a silica gel plug
  5. customThe solvent was removed under reduced pressure
  6. customthe crude product was purified by HPLC purification
  7. washelution from 30 to 100% acetonitrile in water

Sources & evidence

ORD record
ord-bbd07a0ede884d5d916831f0936821d6
Source dataset
uspto-grants-2007_09
Patent number
US07265144B2

Reaction notes

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