Ammonia → HCID 17864574, compound

HRID 1592944Notes

Reaction equation

HRID 1592944 reaction equation
Cl.Br[C:3]1[CH:12]=[C:11]2[C:6]([C:7]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=3)=[N:8][CH:9]=[N:10]2)=[CH:5][C:4]=1[N+:22]([O-:24])=[O:23].[CH3:25][C:26]([N:30]1[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]1)([CH3:29])[C:27]#[CH:28].C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N>CS(C)=O.[Cu](Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(OCC)(=O)C>[Cl:21][C:16]1[CH:15]=[C:14]([NH:13][C:7]2[C:6]3[C:11](=[CH:12][C:3]([C:28]#[C:27][C:26]([CH3:29])([N:30]4[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]4)[CH3:25])=[C:4]([N+:22]([O-:24])=[O:23])[CH:5]=3)[N:10]=[CH:9][N:8]=2)[CH:19]=[CH:18][C:17]=1[F:20]

Participants

10

Reactant 5

HCID 222AmmoniaHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 17864580(7-Bromo-6-nitro-4-quinazolinyl)-(3-chloro-4-fluorophenyl)amine hydrochlorideHCID 22354399HCID 22354399, compound

Product 1

HCID 17864574HCID 17864574, compoundYield 50%

Reagents, catalysts & solvents 4

HCID 24014Cupric ChlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of (7-bromo-6-nitro-4-quinazolinyl)-(3-chloro-4-fluorophenyl)amine hydrochloride (42.0 g, 96.8 mmol), 1-(1,1-dimethyl-2-propynyl)-4-methylpiperazine (4a) (19.3 g, 116 mmol) and triethylamine (47.2 mL, 339 mmol) in DMSO (400 mL) was subjected 3 times to the step of degassing under reduced pressure and then displacement with nitrogen. Copper iodide (I) (460.8 mg, 2.4 mmol), triphenylphosphine (2.53 g, 9.6 mmol) and palladium(II) acetate (543 mg, 2.4 mmol) were added. The mixture was stirred at 80° C. for 9 hrs and allowed to cool to room temperature. The mixture was poured into ethyl acetate (750 mL) and 1% aqueous ammonia solution (1.5 L), and Celite (50 g) was added, which was followed by stirring. Insoluble material was filtered off and the organic layer was washed with brine (500 mL×2) and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and ethyl acetate-methanol mixed solvent (10:1, 130 mL) was added to the residue. The mixture was stirred and the precipitate was collected by filtration. The filtered product was suspension-washed with acetonitrile (100 mL) and dried to give a nitro compound 3a (23.3 g, 48.3 mmol, 50%).

Workup

  1. customof degassing under reduced pressure
  2. temperatureto cool to room temperature
  3. additionwas added
  4. stirringby stirring
  5. filtrationInsoluble material was filtered off
  6. washthe organic layer was washed with brine (500 mL×2)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under reduced pressure and ethyl acetate-methanol mixed solvent (10:1, 130 mL)
  9. additionwas added to the residue
  10. stirringThe mixture was stirred
  11. filtrationthe precipitate was collected by filtration
  12. washThe filtered product was suspension-washed with acetonitrile (100 mL)
  13. customdried

Sources & evidence

ORD record
ord-90e2fce3d6b3406b9668e6e7981db074
Source dataset
uspto-grants-2007_11
Patent number
US07294629B2

Reaction notes

Loading…