N,N-Dimethylpropargylamine → HCID 11668403, compound

HRID 2427642Notes

Reaction equation

HRID 2427642 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:15][CH:14]=1)[CH2:5]2.[CH3:26][N:27]([CH3:31])[CH2:28][C:29]#[CH:30]>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>[CH3:26][N:27]([CH3:31])[CH2:28][C:29]#[C:30][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:15][CH:14]=1)[CH2:5]2

Participants

6

Reactant 2

HCID 81643N,N-DimethylpropargylamineHCID 57949704HCID 57949704, compound

Product 1

HCID 11668403HCID 11668403, compoundYield 62%

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 5-bromo-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.100 g, 0.25 mmol), PdCl2(PPh3)2 (0.009 g, 0.013 mmol), and CuI (0.0025 g, 0.013 mmol) in diisopropylamine (4 mL) was treated with dimethyl-2-propynyl-amine (0.032 mL, 0.3 mmol). The reaction mixture was stirred at 100° C. for 2 h. After the complete consumption of bromo-isoindolone (monitored using GC-MS), the reaction mixture was cooled to ambient temperature and diluted with ethyl acetate (20 mL). The solids were removed by filtration and the filtrate was concentrated. Silica gel column chromatography of the resulting material using combinations of chloroform-methanol (typically 10:1 CHCl3-MeOH) afforded 5-(3-dimethylamino-prop-1-ynyl)-2-(4-phenoxy-benzyl)-2,3-dihydro-isoindol-1-one (0.061 g, 62%). 1H NMR (300 MHz, CDCl3): δ (ppm) 2.36 (s, 6H), 3.47 (s, 2H), 4.25 (s, 2H), 4.76 (s, 2H), 6.94-7.54 (m, 1H), 7.80 (d, 1H). GC-MS: 396 (M)+, 353 (M−43)+.

Workup

  1. customAfter the complete consumption of bromo-isoindolone (monitored using GC-MS)
  2. temperaturethe reaction mixture was cooled to ambient temperature
  3. additiondiluted with ethyl acetate (20 mL)
  4. customThe solids were removed by filtration
  5. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-e5671d1a0b614afa8bfb62a00b8aee0f
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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