1-(Prop-2-yn-1-yl)pyrrolidine → 7-Chloro-2-(4-phenoxy-benzyl)-5-(3-pyrrolidin-1-yl-prop-1-ynyl)-2,3-dihydro-isoindol-1-one

HRID 2427657Notes

Reaction equation

HRID 2427657 reaction equation
[CH2:1]([N:4]1[CH2:8][CH2:7][CH2:6][CH2:5]1)[C:2]#[CH:3].Br[C:10]1[CH:11]=[C:12]2[C:16](=[C:17]([Cl:19])[CH:18]=1)[C:15](=[O:20])[N:14]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:24][CH:23]=1)[CH2:13]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:19][C:17]1[CH:18]=[C:10]([C:3]#[C:2][CH2:1][N:4]2[CH2:8][CH2:7][CH2:6][CH2:5]2)[CH:11]=[C:12]2[C:16]=1[C:15](=[O:20])[N:14]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:24][CH:23]=1)[CH2:13]2

Participants

7

Reactant 3

HCID 2996161-(Prop-2-yn-1-yl)pyrrolidineHCID 21584188Chloroform methanolHCID 579496705-Bromo-7-chloro-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindol-1-one

Product 1

HCID 579495337-Chloro-2-(4-phenoxy-benzyl)-5-(3-pyrrolidin-1-yl-prop-1-ynyl)-2,3-dihydro-isoindol-1-oneYield 66.7%

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-prop-2-ynyl-pyrrolidine (0.024 mL, 0.22 mmol), 5-bromo-7-chloro-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.086 g, 0.20 mmol), PdCl2(PPh3)2 (0.011 g, 0.015 mmol), and CuI (0.0028 g, 0.015 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-2-(4-phenoxy-benzyl)-5-(3-pyrolidin-1-yl-prop-1-ynyl)-2,3-dihydro-isoindol-1-one (0.061 g, 66%). 1H NMR (300 MHz, CDCl3): δ (ppm) 1.83 (m, 4H), 2.65 (m, 4H), 3.64 (s, 2H), 4.23 (s, 2H), 4.76 (s, 2H), 6.93-7.38 (m, 10H), 7.43 (s, 1H).

Sources & evidence

ORD record
ord-1e272f2f02154b788a8416fdb93d2fba
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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