N,N-Dimethylpropargylamine → 7-Chloro-5-(3-dimethylamino-prop-1-ynyl)-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one

HRID 2427659Notes

Reaction equation

HRID 2427659 reaction equation
[CH3:1][N:2]([CH3:6])[CH2:3][C:4]#[CH:5].Br[C:8]1[CH:9]=[C:10]2[C:14](=[C:15]([Cl:17])[CH:16]=1)[C:13](=[O:18])[N:12]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=1)[CH2:11]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:17][C:15]1[CH:16]=[C:8]([C:5]#[C:4][CH2:3][N:2]([CH3:6])[CH3:1])[CH:9]=[C:10]2[C:14]=1[C:13](=[O:18])[N:12]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]([F:30])([F:29])[F:28])=[CH:22][CH:21]=1)[CH2:11]2

Participants

7

Reactant 3

HCID 81643N,N-DimethylpropargylamineHCID 117044755-Bromo-7-chloro-2-(4-trifluoromethoxybenzyl)-2,3-dihydroisoindol-1-oneHCID 21584188Chloroform methanol

Product 1

HCID 115825947-Chloro-5-(3-dimethylamino-prop-1-ynyl)-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-oneYield 103%

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 dimethyl-prop-2-ynyl-amine (0.036 mL, 0.32 mmol), 5-bromo-7-chloro-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.120 g, 0.28 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-5-(3-dimethylamino-prop-1-ynyl)-2-(4-trifluoromethoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.122 g, 79%). 1H NMR (300 MHz, CDCl3): δ (ppm) 2.36 (s, 6H), 3.44 (s, 2H), 4.21 (s, 2H), 4.77 (s, 2H), 7.14-7.36 (m, 5H), 7.43 (s, 1H).

Sources & evidence

ORD record
ord-72301898c8dd4243803b8d8655bc52a3
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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