Lithium Hydroxide → HCID 58958596, compound

HRID 915585Notes

Reaction equation

HRID 915585 reaction equation
C[O:2][C:3](=[O:24])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[CH:7]=[CH:6][C:5]=1[NH:12][C:13]1[N:14]([CH3:23])[N:15]=[C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:17]=1Br.[CH3:25][O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=1.C(Cl)Cl.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Li+]>C1(C)C=CC=CC=1.O1CCOCC1.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]>[C:19]([C:16]1[C:17]([C:30]2[CH:31]=[CH:32][C:27]([O:26][CH3:25])=[CH:28][CH:29]=2)=[C:13]([NH:12][C:5]2[CH:6]=[CH:7][C:8]([O:10][CH3:11])=[CH:9][C:4]=2[C:3]([OH:2])=[O:24])[N:14]([CH3:23])[N:15]=1)([CH3:21])([CH3:22])[CH3:20]

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 58958575HCID 58958575, compound

Product 1

HCID 58958596HCID 58958596, compoundYield 27.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
75 °C

Procedure

To a solution 2-(4-bromo-5-tert-butyl-2-methyl-2H-pyrazol-3-ylamino)-5-methoxybenzoic acid methyl ester (Example 96, 100 mg, 0.25 mmol), 4-methoxyphenylboronic acid (153.4 mg, 1.01 mmol), PdCl2(dppf).CH2Cl2 (18.46 mg, 0.03 mmol) in a mixture of toluene (6.1 mL) and dioxane (1.22 mL) was added a 2M aqueous solution of sodium carbonate (1.22 mL, 2.44 mmol). A flow of Ar was passed through the reaction mixture for 15 min, and then the reaction was stirred at 75° C. for 18 h. The reaction mixture was then cooled to rt, and filtered through a plug of silica gel. The filtrate was concentrated under reduced pressure, and then the residue was dissolved in a mixture of THF (4 mL), MeOH (2 mL) and water (4 mL). Lithium hydroxide (60 mg, 2.52 mmol) was added, and the mixture was stirred at rt for 18 h. The reaction mixture was then concentrated and the residue purified by preparative HPLC to give the title compound (27.9 mg, 27%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.21 (s, 9H), 3.61 (s, 3H), 3.74 (s, 6H), 6.41 (d, 1H), 6.70 (d, 2H), 7.04 (dd, 1H), 7.09 (d, 2H), 7.39 (d, 1H). ES-MS m/z 410.2 (MH+); HPLC RT (min) 3.66.

Workup

  1. temperatureThe reaction mixture was then cooled to rt
  2. filtrationfiltered through a plug of silica gel
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. dissolutionthe residue was dissolved in a mixture of THF (4 mL), MeOH (2 mL) and water (4 mL)
  5. stirringthe mixture was stirred at rt for 18 h
  6. concentrationThe reaction mixture was then concentrated
  7. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-4af2db72b5b84fe4994d4a57f82b42b8
Source dataset
uspto-grants-2007_09
Patent number
US07265144B2

Reaction notes

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