Diisopropylamine → HCID 68882095, compound

HRID 1785186Notes

Reaction equation

HRID 1785186 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:27][CH2:28][CH2:29][CH2:30][Cl:31])=[CH:20][C:21]=2[O:23][CH:24]([CH3:26])[CH3:25])[N:16]=[CH:15][N:14]=1.[CH3:32][O:33][CH2:34][C:35]#[CH:36].C(NC(C)C)(C)C>[Cu]I.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]([C:36]#[C:35][CH2:34][O:33][CH3:32])[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:27][CH2:28][CH2:29][CH2:30][Cl:31])=[CH:20][C:21]=2[O:23][CH:24]([CH3:26])[CH3:25])[N:16]=[CH:15][N:14]=1

Participants

6

Reactant 3

HCID 7912DiisopropylamineHCID 693933-MethoxypropyneHCID 68881262HCID 68881262, compound

Product 1

HCID 68882095HCID 68882095, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
-10 °C

Procedure

A mixture N-(5-chloro-7-iodo-1,3-benzodioxol-4yl)-7-(3-chloropropoxy)-5-isopropoxyquinazolin-4-amine (1.313 g, 1:1 wt.:wt. mixture with triphenylphosphine), 3-methoxy-prop-1-yne (0.19 ml), palladium(II) bis-triphenylphosphine dichloride (0.080 g) and copper (I) iodide (0.022 g) was taken up into ethyl acetate (15 ml) and cooled to −10° C. This was set to stir rapidly and then diisopropylamine (0.32 ml) was added and the reaction was stirred cold for 45 minutes before being warmed to room temperature and left to stir for a further 90 minutes. The reaction mixture was then filtered through Celite under suction (washing the Celite with a further portion of ethyl acetate) then the combined filtrate solutions were evaporated under reduced pressure to leave a brown gum. The gum was then purified by column chromatography on silica using diethyl ether as eluent. There was thus obtained the title compound (as a 1:1.3 wt.:wt. mixture with triphenylphosphine) (1.056 g) as a yellow solid; NMR Spectrum: (CDCl3) 1.53 (d, 6H), 2.30 (quin, 2H), 3.45 (s, 3H), 3.76 (t, 2H), 4.25 (t, 2H), 4.35 (s, 2H), 4.83 (sept, 1H), 6.10 (s, 2H), 6.49 (d, 1H), 6.85 (d, 1H), 7.06 (s, 1H), 8.52 (s, 1H), 9.42 (s, 1H)—triphenylphosphine 7.46 (m, 6H), 7.54 (m, 3H), 7.67 (m, 6H);

Workup

  1. stirringthe reaction was stirred cold for 45 minutes
  2. temperaturebefore being warmed to room temperature
  3. waitleft
  4. stirringto stir for a further 90 minutes
  5. filtrationThe reaction mixture was then filtered through Celite under suction (
  6. washwashing the Celite with a further portion of ethyl acetate) then the combined filtrate solutions
  7. customwere evaporated under reduced pressure
  8. customto leave a brown gum
  9. customThe gum was then purified by column chromatography on silica

Sources & evidence

ORD record
ord-edbd85ba39e64e66a26324c30e4b33d9
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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