Dimethylformamide → HCID 68880877, compound

HRID 1785150Notes

Reaction equation

HRID 1785150 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][C@H:33]([CH3:35])[O:32][C@H:31]([CH3:36])[CH2:30]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1.[CH3:37][N:38]([CH3:45])[C:39]([NH:41][CH2:42][C:43]#[CH:44])=[O:40].CN(C=O)C>C(OCC)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:1][C:2]1[CH:10]=[C:9]([C:44]#[C:43][CH2:42][NH:41][C:39](=[O:40])[N:38]([CH3:45])[CH3:37])[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][C@H:33]([CH3:35])[O:32][C@H:31]([CH3:36])[CH2:30]3)=[C:20]([O:23][CH3:24])[CH:21]=2)[N:16]=[CH:15][N:14]=1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 44190381Urea, N,N-dimethyl-N-2-propynyl- (9CI)HCID 68881234HCID 68881234, compound

Product 1

HCID 68880877HCID 68880877, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

N-(5-Chloro-7-iodo-1,3-benzodioxol-4-yl)-7-[3-(cis-2,6-dimethylmorpholin-4-yl)propoxy]-6-methoxyquinazolin-4-amine (250 mg, 0.40 mmol) and N,N-dimethyl-N′-prop-2-yn-1-ylurea (100 mg, 0.79 mmol) in ethyl acetate (8 ml) stirred at room temperature, under an atmosphere of nitrogen, and treated with bis(triphenylphosphine)palladium(II) dichloride (28 mg, 10 mol %) followed by copper(I) iodide (8 mg, 10 mol %) and diisopropylamnine (81 mg, 0.81 mmol). The reaction was stirred 1 hr then DMF (4 ml) added and the reaction stirred for a further 1 hr. The resulting orange solution was evaporated in vacuo then treated with dilute aqueous sodium bicarbonate solution and extracted with dichloromethane. The extract was dried over magnesium sulphate and evaporated to an orange oil. Purification was by column chromatography on silica using increasing concentrations of methanolic ammonia in dichloromethane as eluent gave the title compound (211 mg, 85%) as a pale orange solid;

Workup

  1. stirringthe reaction stirred for a further 1 hr
  2. customThe resulting orange solution was evaporated in vacuo
  3. additionthen treated with dilute aqueous sodium bicarbonate solution
  4. extractionextracted with dichloromethane
  5. dry with materialThe extract was dried over magnesium sulphate
  6. customevaporated to an orange oil
  7. customPurification
  8. temperatureincreasing concentrations of methanolic ammonia in dichloromethane as eluent

Sources & evidence

ORD record
ord-a4998f02435349f59d1147a68dc10e89
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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