Diisopropylamine → N-[3-(6-chloro-7-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]-N,N',N'-trimethylurea

HRID 1785133Notes

Reaction equation

HRID 1785133 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[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1.[CH3:35][N:36]([CH3:44])[C:37]([N:39]([CH3:43])[CH2:40][C:41]#[CH:42])=[O:38].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>[Cl:1][C:2]1[CH:10]=[C:9]([C:42]#[C:41][CH2:40][N:39]([CH3:43])[C:37]([N:36]([CH3:44])[CH3:35])=[O:38])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:12][C:13]1[C:22]2[C:17](=[CH:18][C:19]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 15065504N,N,N'-trimethyl-N'-prop-2-yn-1-ylureaHCID 68884527N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

Product 1

HCID 68881445N-[3-(6-chloro-7-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}-1,3-benzodioxol-4-yl)prop-2-yn-1-yl]-N,N',N'-trimethylureaYield 69%

Reagents, catalysts & solvents 3

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

Procedure

This was prepared using the method described in example 26 but it was carried out at room temperature over 3 hr using N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4ylpropoxy)quinazolin-4-amine (310 mg, 0.52 mmol), N,N,N′-trimethyl-N′-prop-2-yn-1-ylurea (145 mg, 1.04 mmol), bis(triphenylphosphine) palladium(II) dichloride (36 mg, 10 mol %), copper(I) iodide (10 mg, 10 mol %) and diisopropylamine (105 mg, 1.04 mmol) in ethyl acetate (10 ml). The crude product was purified by column chromatography on silica using increasing concentrations of methanol in dichloromethane as eluent to give the title compound (218 mg, 69%) as a pale brown solid; NMR Spectrum:(CDCl3) 2;11 (quintet, 2H), 2.48 (m, 4H), 2.56 (t, 2H), 2.87 (s, 6H), 2.92 (s, 3H), 3.72 (m, 4H), 4.00 (s, 3H), 4.15 (s, 2H), 4.25 (t, 2H), 6.06 (s, 2H), 7.03 (s, 1H), 7.10-7.30 (s(broad), 1H), 7.20 (s, 1H), 7.31 (s, 1H), 8.60 (s, 1H); Mass Spectrum: M+H+ 611/613.

Workup

  1. customThis was prepared
  2. customThe crude product was purified by column chromatography on silica using
  3. temperatureincreasing concentrations of methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-51058237535e457d9905830a9a214c22
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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