Toluene → HCID 86710184, compound

HRID 2284417Notes

Reaction equation

HRID 2284417 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[N:7][C:8]([Cl:12])=[N:9]2)=[CH:4][CH:3]=1.[NH2:19][C:20]1[CH:21]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:24][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>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.O.C(O)C>[Cl:12][C:8]1[N:7]=[C:6]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:5]2[C:10](=[CH:11][C:2]([C:24]3[CH:25]=[C:20]([CH:21]=[CH:22][CH:23]=3)[NH2:19])=[CH:3][CH:4]=2)[N:9]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27346553-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 866657584-(7-Bromo-2-chloroquinazolin-4-yl)morpholine

Product 1

HCID 86710184HCID 86710184, compoundYield 63.6%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 50 mL round bottom flask, 4-(7-bromo-2-chloroquinazolin-4-yl)morpholine (1.0 g, 0.0030 mol—Preparation 1), 3-aminophenylboronic acid pinacol ester (0.657 g, 0.0030 mol), sodium carbonate (0.635 g, 0.0060 mol), toluene (20 mL), ethanol (4 mL) and water (3 mL) were added. The reaction mixture was degassed with N2 for 5-10 minutes. To the same reaction mixture, Pd(PPh3)2Cl2 (0.105 g, 0.00015 mol) was added and degassed with N2 for 5-10 minutes. The reaction mixture was stirred at 95° C. for 2 hours. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure to afford the crude product. The crude product was purified by flash column chromatography (40% ethyl acetate in hexane) to provide the title compound (0.65 g, 62%). 1H NMR (400 MHz, CDCl3): δ 8.00 (d, J=1.6 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 7.66 (dd, J′=8.4 Hz, J″=1.6 Hz, 1H), 7.30 (d, J=7.6 Hz, 1H), 7.08 (d, J=8.0 Hz, 1H), 6.99 (t, J=2.0 Hz, 1H), 6.77 (dd, J′=7.6 Hz, J″=1.2 Hz, 1H), 3.90 (s, 8H), 3.84 (br s, 2H), LC-MS (ESI): Calculated mass. 340.11, Observed mass [M+H]+: 341.1 (RT=0.48 min).

Workup

  1. customThe reaction mixture was degassed with N2 for 5-10 minutes
  2. customdegassed with N2 for 5-10 minutes
  3. temperatureThe reaction mixture was cooled
  4. additiondiluted with ethyl acetate
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated under reduced pressure
  8. customto afford the crude product
  9. customThe crude product was purified by flash column chromatography (40% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ba53fd419356468d9280809f7517a62f
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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