Diisopropylamine → N-[5-chloro-7-({1-[(4-methylphenyl)sulfonyl]-1H-pyrazol-5-yl}ethynyl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

HRID 1785166Notes

Reaction equation

HRID 1785166 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]#[CH:12])[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[C:21]([O:24][CH3:25])[CH:22]=2)[N:17]=[CH:16][N:15]=1.I[C:37]1[N:41]([S:42]([C:45]2[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=2)(=[O:44])=[O:43])[N:40]=[CH:39][CH:38]=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:11]#[C:12][C:37]2[N:41]([S:42]([C:45]3[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=3)(=[O:43])=[O:44])[N:40]=[CH:39][CH:38]=2)[C:5]2[O:6][CH2:7][O:8][C:4]=2[C:3]=1[NH:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:31][CH2:32][O:33][CH2:34][CH2:35]3)=[C:21]([O:24][CH3:25])[CH:22]=2)[N:17]=[CH:16][N:15]=1

Participants

7

Reactant 3

HCID 7912DiisopropylamineHCID 159327945-iodo-1-tosyl-1H-pyrazoleHCID 86601565N-(5-chloro-7-ethynyl-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine

Product 1

HCID 68883671N-[5-chloro-7-({1-[(4-methylphenyl)sulfonyl]-1H-pyrazol-5-yl}ethynyl)-1,3-benzodioxol-4-yl]-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amineYield 51.3%

Reagents, catalysts & solvents 3

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

Procedure

A solution of N-(5-chloro-7-ethynyl-1,3-benzodioxol-4-yl)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine (0.140 g, 0.28 mmol ), 5-iodo-1-[(4-methylphenyl)sulfonyl)-1H-pyrazole (0.147 g, 0.42 mmol) and diisopropylamine (0.078 ml, 0.56 mmol) in ethyl acetate (5 ml) was cooled to −20 C under a nitrogen atmosphere. To this mixture was added copper (I) iodide (0.016 g, 0.084 mmol) and bis(triphenylphospine)palladium (II) chloride (0.039 g, 0.056 mmol). The reaction mixture was allowed to warm to ambient temperature and then stirred overnight. The reaction mixture was filtered and then evaporated under reduced pressure. The residue was purified by flash chromatography on silica eluting with a mixture of 0-8% methanol in dichloromethane to give the product as a yellow solid (0.103 g, 51%). Mass Spectrum: M+H+ 717 and M+H− 715.

Workup

  1. filtrationThe reaction mixture was filtered
  2. customevaporated under reduced pressure
  3. customThe residue was purified by flash chromatography on silica eluting with a mixture of 0-8% methanol in dichloromethane

Sources & evidence

ORD record
ord-040cac7a9c584dd08573d99a3cb4cd8a
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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