Toluene → HCID 86665776, compound

HRID 2284413Notes

Reaction equation

HRID 2284413 reaction equation
Br[C:2]1[CH:11]=[N:10][C:9]2[C:8]([N:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:7][C:6]([Cl:18])=[N:5][C:4]=2[CH:3]=1.[CH:19]([C:21]1[O:25][C:24](B(O)O)=[CH:23][CH:22]=1)=[O:20].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:18][C:6]1[N:7]=[C:8]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[N:10]=[CH:11][C:2]([C:24]3[O:25][C:21]([CH:19]=[O:20])=[CH:22][CH:23]=3)=[CH:3][C:4]=2[N:5]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 27343555-Formylfuran-2-boronic acidHCID 86665768HCID 86665768, compound

Product 1

HCID 86665776HCID 86665776, compoundYield 73.5%

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-chloropyrido[3,2-d]pyrimidin-4-yl)morpholine (0.5 g, 0.0015 mol—Preparation 3), 5-formyl-2-furanylboronic acid (0.21 g, 0.0015 mol), sodium carbonate (0.32 g, 0.003 mol), toluene (20 mL), ethanol (10 mL) and water (5 mL) were added. The reaction vessel was degassed with N2 for 5-10 minutes. To the same reaction mixture, Pd(PPh3)2Cl2 (0.053 g, 0.000075 mol) was added and 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 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 by column chromatography (60-120 silica gel, 60% ethyl acetate in n-hexane) to yield the desired product (0.38 g, 72%). 1H NMR (300 MHz, CDCl3): δ 9.77 (s, 1H), 9.12 (d, J=2.1 Hz, 1H), 8.34 (d, J=2.1 Hz, 1H), 7.40 (d, J=3.6 Hz, 1H), 7.11 (d, J=3.6 Hz, 1H), 4.50 (br s, 4H), 3.91-3.88 (m, 4H): LC-MS (ESI): Calculated mass: 344.0; Observed mass [M+H]+: 345.0 (RT=1.39 min).

Workup

  1. customThe reaction vessel was degassed with N2 for 5-10 minutes
  2. customagain degassed 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 sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customto afford the crude product
  9. customThe crude product was purified by column chromatography (60-120 silica gel, 60% ethyl acetate in n-hexane)

Sources & evidence

ORD record
ord-c669a519b093440e9a26610a7b92fa38
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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