Dimethylformamide → 2-Chloro-6-fluoro-4-morpholin-4-yl-7-pyridin-3-yl-quinazoline

HRID 2092548Notes

Reaction equation

HRID 2092548 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][C:3]=1[F:19].[N:20]1[CH:25]=[CH:24][CH:23]=[C:22](B(O)O)[CH:21]=1.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:22]3[CH:21]=[N:20][CH:25]=[CH:24][CH:23]=3)=[C:3]([F:19])[CH:4]=2)[N:9]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 866657622-Chloro-4-morpholino-6-fluoro-7-bromo-quinazoline

Product 1

HCID 866657642-Chloro-6-fluoro-4-morpholin-4-yl-7-pyridin-3-yl-quinazolineYield 100.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 50 mL round bottom flask, 7-bromo-2-chloro-6-fluoro-4-morpholin-4-yl-quinazoline (200 mg, 0.0005764 mol), pyridine-3-boronic acid (63.3 mg, 0.0005188 mol), sodium carbonate (152.6 mg, 0.001441 mol), DMF (10 mL) and water (5 mL) were added and degassed the reaction vessel with nitrogen for 5-10 min. To the same reaction mixture, Pd(PPh3)2Cl2 (20.1 mg, 0.0000288 mol) was added and again degassed with N2 for 5-10 min. The reaction mixture was stirred at 95° C. for 2 h. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was removed under reduced pressure to afford the crude product. The crude product was purified using column chromatography (60-120 silica gel, 2% MeOH in chloroform) to yield the desired product (180 mg, 91%). 1H NMR (300 MHz, CD3OD): δ 8.27-8.30 (m, 1H), 8.21-8.25 (m, 1H), 8.15-8.18 (m, 1H), 7.91-7.92 (m, 1H), 7.74-7.78 (m, 1H), 7.47-7.51 (m, 1H), 3.99-4.01 (m, 4H), 3.85-3.88 (m, 4H); LC-MS (ESI): Calculated mass: 344.1; Observed mass: 344.9 [M+H]+ (RT: 1.3 min).

Workup

  1. customdegassed the reaction vessel with nitrogen for 5-10 min
  2. customagain degassed with N2 for 5-10 min
  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 sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customto afford the crude product
  9. customThe crude product was purified

Sources & evidence

ORD record
ord-6bf59c145f77402f963b1e52441a1287
Source dataset
uspto-grants-2013_05
Patent number
US08440662B2

Reaction notes

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