Diisopropylamine → N-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]morpholine-4-carboxamide

HRID 1785113Notes

Reaction equation

HRID 1785113 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9](I)[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH2:12].[CH2:13]([NH:16][C:17]([N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)=[O:18])[C:14]#[CH:15].C(NC(C)C)(C)C>C(OCC)(=O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[NH2:12][C:3]1[C:4]2[O:8][CH2:7][O:6][C:5]=2[C:9]([C:15]#[C:14][CH2:13][NH:16][C:17]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])=[CH:10][C:2]=1[Cl:1]

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 179805275-Chloro-7-iodo-1,3-benzodioxol-4-amineHCID 45088989N-(prop-2-yn-1-yl)morpholine-4-carboxamide

Product 1

HCID 68881313N-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]morpholine-4-carboxamideYield 78%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

5-Chloro-7-iodo-1,3-benzodioxol-4-amine (600 mg, 2.02 mmol) and N-prop-2-yn-1-ylmorpholine-4-carboxamide (406 mg, 2.42 mmol) in ethyl acetate (10 ml) were cooled in ice-methanol, under an atmosphere of nitrogen, and then treated with bis(triphenylphosphine) palladium(II) dichloride (140 mg, 10 mol %) followed by copper(I) iodide (38 mg, 10 mol %) and diisopropylamine (407 mg, 4.03 mmol). The reaction was allowed to warm to room temperature and stirred for 3 hours and then filtered through Celite. The filtrate was purified by column chromatography on silica using ethyl acetate as eluent to give N-[3-(7-amino-6-chloro-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]morpholine-4-carboxamide (529 mg, 78%) as a pale brown solid; NMR Spectrum:(DMSOd6) 3.28 (m, 4H), 3.54 (m, 4H), 4.05 (d, 2H), 5.47 (s, 2H), 6.05 (s, 2H), 6.78 (s, 1H), 7.01 (t, 1H); Mass Spectrum: M+H+ 338/340.

Workup

  1. filtrationfiltered through Celite
  2. customThe filtrate was purified by column chromatography on silica

Sources & evidence

ORD record
ord-1fcb2972fcc543b897ea9b26af6fc289
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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