Bromobenzene → HCID 68670937, compound

HRID 571950Notes

Reaction equation

[NH2:1][C:2]1[CH:14]=[C:13]([N:15]2[CH2:20][CH2:19][N:18]([CH3:21])[CH2:17][CH2:16]2)[CH:12]=[CH:11][C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].Br[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1(C)C=CC=CC=1.ClCCl.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:21][N:18]1[CH2:19][CH2:20][N:15]([C:13]2[CH:12]=[CH:11][C:3]([C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])=[C:2]([NH:1][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH:14]=2)[CH2:16][CH2:17]1

Participants

Conditions

Temperature: 100 °C

Procedure

In a dry Schlenk tube under argon atmosphere tert-butyl 2-amino-4-(4-methylpiperazin-1-yl)benzoate (800 mg, 2.745 mmol) was dissolved in dry toluene (14 mL). Argon was bubbled through the mixture for a few minutes before adding bromobenzene (0.32 mL, 3.02 mmol, 1.1 eq), Cs2CO2 (1.34 g, 4.118 mmol, 1.5 eq), Pd(OAc)2 (16 mg, 0.069 mmol, 2.5 mol %) and Rac-BINAP (88 mg, 0.137 mmol, 5 mol %). The mixture was then stirred at 100° C. for 21 hours. The mixture was allowed to cool to room temperature and diluted with dichloromethane. Salts were filtered over a Celite pad and the filtrate was concentrated under reduced pressure. The crude product was purified by chromatography over silica gel (DCM/EtOH/NH3 7% in methanol 95:5:0.5) to give 1.13 g of title compound (quant. yield) as off-white solid

Workup

customArgon was bubbled through the mixture for a few minutes
temperatureto cool to room temperature
filtrationSalts were filtered over a Celite pad
concentrationthe filtrate was concentrated under reduced pressure
customThe crude product was purified by chromatography over silica gel (DCM/EtOH/NH3 7% in methanol 95:5:0.5)

Sources & evidence

ORD record: ord-9ec389436b1a431b9dd17165eb0ae4b8
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029356B2

Reaction notes

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