Cesium carbonate → HCID 68904647, compound

HRID 900142Notes

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

(5Bromo-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 ovemight 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-b3c4a1a405ee4d82b86c77765cbfc6b7
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07358253B2

Reaction notes

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