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

HRID 1785159Notes

Reaction equation

HRID 1785159 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.[CH:35](NC(C)C)([CH3:37])[CH3:36].C(OCC)(=[O:44])C>[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:1][C:2]1[CH:10]=[C:9]([C:36]#[C:35][CH2:37][OH:44])[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

6

Reactant 3

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 68884527N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

Product 1

HCID 688839543-(6-Chloro-7-{[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-yl]amino}-1,3-benzodioxol-4-yl)prop-2-yn-1-olYield 51%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst

Procedure

A solution of N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine (0.35 g, 0.59 mmol) propargyl alcohol (0.075 ml, 1.3 mmol) and diisopropylamine (0.18 ml, 1.3 mmol) in ethyl acetate (10 ml) was cooled to −20 C under a nitrogen atmosphere. To this was added copper (I) iodide (0.034 g, 0.12 mmol) and bis(triphenylphospine)palladium (II) chloride (0.082 g, 0.17 mmol). The reaction was allowed to warm to ambient temperature and then stirred overnight. The reaction was filtered through Celite and the filtrate was then evaporated under reduced pressure. The residue was purified by flash chromatography on silica eluting with a mixture of 0-10% methanol in dichloromethane to give the product as a solid (0.16 g, 51%). NMR Spectrum: (DMSOd6) 1.95 (m, 2H), 2.5 (s(broad), 4H), 2.61 (t, 2H), 3.61 (t, 4H), 3.92 (s, 3H), 4.21 (t, 2H), 4.37 (s, 2H), 5.02 (s(broad), 1H), 6.06 (s, 2H), 7.07 (s, 1H), 7.17 (s, 1H), 7.83 (s, 1H), 8.25 (s(broad), 1H), 9.18 (s(broad), 1H). Mass Spectrum: M+H+ 527 and M+H− 525.

Workup

  1. filtrationThe reaction was filtered through Celite
  2. customthe filtrate was then evaporated under reduced pressure
  3. customThe residue was purified by flash chromatography on silica eluting with a mixture of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-abd2f4179249463d84bddcf087027373
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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