Diisopropylamine → N-[5-chloro-7-(phenylethynyl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

HRID 1785160Notes

Reaction equation

HRID 1785160 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.[C:35]1([C:41]#[CH:42])[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.C(NC(C)C)(C)C>C(OCC)(=O)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:42]#[C:41][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[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 10821PhenylacetyleneHCID 68884527N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

Product 1

HCID 68884804N-[5-chloro-7-(phenylethynyl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amineYield 66.1%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine (0.17 g, 0.285 mmol), phenyl acetylene (0.07 ml, 0.63 mmol) and diisopropylamine (0.088 ml, 0.63 mmol) in ethyl acetate (4 ml) was cooled to −20 C under a nitrogen atmosphere. To this was added copper (I) iodide (0.016 g, 0.085 mmol) and bis(triphenylphospine)palladium (II) chloride (0.04 g, 0.057 mmol). The mixture was allowed to warm to ambient temperature and then stirred overnight. The mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography on silica eluting with a mixture of 0-10% methanol in dichloromethane gave the product as a solid (0.108 g, 66%). NMR Spectrum: (DMSOd6 at 373k+d4 acetic acid) 2.10 (m, 2H), 2.76 (t, 4H), 2.83 (t, 2H), 3.69 (t, 4H), 3.97 (s, 3H), 4.24 (t, 2H), 6.12 (s, 2H), 7.15 (s, 1H), 7.30 (s(broad), 1H), 7.42 (m, 3H), 7.54 (m, 2H), 7.95 (s, 1H), 8.63 (s(broad), 1H). Mass Spectrum: M+H+ 573 and M+H− 571.

Workup

  1. temperaturewas cooled to −20 C under a nitrogen atmosphere
  2. filtrationThe mixture was filtered
  3. customthe filtrate was evaporated under reduced pressure
  4. customThe residue was purified by flash chromatography on silica eluting with a mixture of 0-10% methanol in dichloromethane

Sources & evidence

ORD record
ord-831c118a627246c8bcd8b1ee325f0ad3
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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