5-Bromo-7-chloro-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindol-1-one → 7-Chloro-5-[3-(4-methyl-piperazin-1-yl)-prop-1 ynyl)-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427661Notes

Reaction equation

HRID 2427661 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]#[CH:10])[CH2:4][CH2:3]1.Br[C:12]1[CH:13]=[C:14]2[C:18](=[C:19]([Cl:21])[CH:20]=1)[C:17](=[O:22])[N:16]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1)[CH2:15]2.C(Cl)(Cl)Cl.CO>C(NC(C)C)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:21][C:19]1[CH:20]=[C:12]([C:10]#[C:9][CH2:8][N:5]2[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]2)[CH:13]=[C:14]2[C:18]=1[C:17](=[O:22])[N:16]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:31])[F:32])=[CH:26][CH:25]=1)[CH2:15]2

Participants

7

Reactant 3

HCID 116328075-Bromo-7-chloro-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindol-1-oneHCID 135140911-Methyl-4-(prop-2-yn-1-yl)piperazineHCID 21584188Chloroform methanol

Product 1

HCID 579493907-Chloro-5-[3-(4-methyl-piperazin-1-yl)-prop-1 ynyl)-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindol-1-oneYield 90.2%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 7912DiisopropylamineSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 1-methyl-4-prop-2-ynyl-piperazine (0.122 mL, 0.79 mmol), 5-bromo-7-chloro-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindol-1-one (0.240 g, 0.6 mmol), PdCl2(PPh3)2 (0.023 g, 0.03 mmol), and CuI (0.006 g, 0.03 mmol) in diisopropyl amine (4 mL) was stirred at 100° C. for 2 h. Workup and silica gel column chromatography using 10:1 CHCl3-MeOH afforded 7-chloro-5-[3-(4-methyl-piperazin-1-yl)-prop-1 ynyl)-2-(4-trifluoromethyl-benzyl)-2,3-dihydro-isoindol-1-one (0.250 g, 90%). 1H NMR (300 MHz, CDCl3): δ (ppm) 2.34 (s, 3H), 2.32-2.54 (m, 8H), 3.57 (s, 2H), 4.20 (s, 2H), 4.81 (s, 2H), 7.34 (s, 1H), 7.41-7.63 (m, 5H).

Sources & evidence

ORD record
ord-3875fcf3ba02468583a6749d53967f56
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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