Diisopropylamine → HCID 10258047, compound

HRID 1785187Notes

Reaction equation

HRID 1785187 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][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[CH:20][C:21]=2[O:23][CH:24]([CH3:26])[CH3:25])[N:16]=[CH:15][N:14]=1.[C:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1)#[CH:38].C(NC(C)C)(C)C>[Cu]I.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]([C:38]#[C:37][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=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:27][CH2:28][CH2:29][CH2:30][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)=[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 137268EthynylpyridineHCID 68881758HCID 68881758, compound

Product 1

HCID 10258047HCID 10258047, 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

N-(5-chloro-7-iodo-1,3-benzodioxol-4-yl)-5-isopropoxy-7-(3-morpholin-4-ylpropoxy)quinazolin-4-amine (0.162 g), 2-ethynyl pyridine (0.03 ml), palladium(II) bis-triphenylphosphine dichloride (0.020 g) and copper (I) iodide (0.006 g) was taken up into ethyl acetate (5 ml) and cooled to −10° C. This was set to stir rapidly, then diisopropylamine (0.047 ml) was added and the reaction was stirred cold for 30 minutes before being warmed to room temperature and left to stir for 18 hours. 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 give a brown gum. This was then purified by column chromatography on silica using increasingly polar mixtures of methanol in dichloromethane as eluent. There was thus obtained the title compound (0.090 g) as a pale brown foam; NMR Spectrum: (CDCl3) 1.54 (d, 6H), 2.04 (quin, 2H), 2.50 (m, 4H), 2.56 (t, 2H), 3.74 (t, 4H), 4.16 (t, 2H), 4.83 (sept, 1H), 6.14 (s, 2H), 6.50 (d, 1H), 6.84 (d, 1H), 7.19 (s, 1H), 7.25 (m, 1H), 7.54 (d, 1H), 7.68 (td, 1H), 8.53 (s, 1H), 8.63 (dd, 1H), 9.46 (s, 1H); Mass Spectrum: M+H+ 602/604.

Workup

  1. stirringthe reaction was stirred cold for 30 minutes
  2. temperaturebefore being warmed to room temperature
  3. waitleft
  4. stirringto stir for 18 hours
  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 give a brown gum
  9. customThis was then purified by column chromatography on silica using
  10. temperatureincreasingly polar mixtures of methanol in dichloromethane as eluent

Sources & evidence

ORD record
ord-adf8a5f18ab64cb8bd065a96ba1a48e4
Source dataset
uspto-grants-2009_03
Patent number
US07504408B2

Reaction notes

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