Dimethylformamide → 4-(2-Chloro-7-(3-(methylsulfonyl)phenyl)quinazolin-4-yl)morpholine

HRID 2284401

Reaction equation

HRID 2284401 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.[CH3:19][S:20]([C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1)(=[O:22])=[O:21].C(=O)([O-])[O-].[Na+].[Na+].CN(C=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.O>[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:27]3[CH:26]=[CH:25][CH:24]=[C:23]([S:20]([CH3:19])(=[O:22])=[O:21])[CH:28]=3)=[CH:3][CH:4]=2)[N:9]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 866657584-(7-Bromo-2-chloroquinazolin-4-yl)morpholine

Product 1

HCID 866657604-(2-Chloro-7-(3-(methylsulfonyl)phenyl)quinazolin-4-yl)morpholineYield 82.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 50 mL round bottom flask, 4-(7-bromo-2-chloroquinazolin-4-yl)morpholine (0.25 g, 0.0007 mol—Preparation 1), 3-methylsulfonylphenylboronic acid (0.137 g, 0.0006 mol), sodium carbonate (0.121 g, 0.00105 mol), DMF (8 mL) and water (2 mL) were added. The reaction vessel was degassed with N2 for 5-10 minutes. To the same reaction mixture, Pd(PPh3)2Cl2 (0.027 g, 0.000035 mol) was added and the mixture again degassed with N2 for 5-10 minutes. The reaction mixture was stirred at 95° C. for 2 hours. The reaction mixture was cooled and water was added. The crude product was extracted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was removed under the reduced pressure to afford the crude product. The crude product was purified by column chromatography (60-120 silica gel, 50-100% ethyl acetate in n-hexane) to provide the desired product (0.2 g, 65%). 1H NMR (300 MHz, CDCl3): δ 8.25 (br s, 1H), 8.06-7.94 (m, 3H), 7.75-7.46 (m, 3H), 3.93 (br s, 4H), 3.91 (br s, 4H), 3.12 (s, 3H): LC-MS (ESI): Calculated mass: 403.0; Observed mass [M+H]+: 404.0 (RT=1.30 min).

Workup

  1. customThe reaction vessel was degassed with N2 for 5-10 minutes
  2. customthe mixture again degassed with N2 for 5-10 minutes
  3. temperatureThe reaction mixture was cooled
  4. additionwater was added
  5. extractionThe crude product was extracted with ethyl acetate
  6. washThe organic layer was washed with water, brine
  7. dry with materialdried over sodium sulfate
  8. customThe solvent was removed under the reduced pressure
  9. customto afford the crude product
  10. customThe crude product was purified by column chromatography (60-120 silica gel, 50-100% ethyl acetate in n-hexane)

Sources & evidence

ORD record
ord-160757d439134489af649a18f881bef3
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Linked notes

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