Cesium carbonate → HCID 68904647, compound

HRID 493725Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[C:9](Br)[CH:8]=[C:7]([CH3:12])[C:6]=1[Cl:13].[CH3:15][N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:10]=[C:9]([N:19]2[CH2:20][CH2:21][N:16]([CH3:15])[CH2:17][CH2:18]2)[CH:8]=[C:7]([CH3:12])[C:6]=1[Cl:13]

Participants

Conditions

Temperature: 100 °C

Procedure

(5-Bromo-2-chloro-3-methyl-phenyl)-acetic acid methyl ester (2.0 g, 7.2 mmol), N-methylpiperazine (960 μL, 8.6 mmol) and Cs2CO3 (3.3 g, 10.1 mmol) are suspended in toluene (80 mL). Pd(OAc)2 (81 mg, 0.36 mmol) and BINAP (224 mg, 0.36 mmol) are added and the reaction is stirred at 100° C. overnight. The mixture is filtered through Celite and the solvent is evaporated. The residue is purified by FCC (AcOEt/AcOH/H2O 60:15:15) to afford 2-[2-chloro-3-methyl-5-(4-methyl-piperazin-1-yl)-phenyl]-acetic acid methyl ester. The ester is suspended in NH4OH 25% (60 mL). The mixture is stirred overnight at RT and the precipitate is filtered off to yield the amide. 1H NMR (DMSO, 400 MHz) δ 2.20 (s, 3H), 2.27 (s, 3H), 2.40-2.45 (m, 4H), 3.07-3.13 (m, 4H), 3.48 (s, 2H), 6.78 (s, 1H), 6.82 (s, 1H), 6.91 (br s, 1H), 7.34 (br s, 1H).

Workup

filtrationThe mixture is filtered through Celite
customthe solvent is evaporated
customThe residue is purified by FCC (AcOEt/AcOH/H2O 60:15:15)

Sources & evidence

ORD record: ord-36526c3f4b414a818a4264fae1df6e73
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07534808B2

Reaction notes

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