Toluene → HCID 86710174, compound

HRID 2284406Notes

Reaction equation

HRID 2284406 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.[C:19]([NH:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1)(=[O:21])[CH3:20].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:27]3[CH:28]=[C:23]([NH:22][C:19](=[O:21])[CH3:20])[CH:24]=[CH:25][CH:26]=3)=[CH:3][C:4]=2[N:5]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 157274(3-Acetamidophenyl)boronic acidHCID 86665768HCID 86665768, compound

Product 1

HCID 86710174HCID 86710174, compoundYield 78.8%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 100 mL round bottom flask, 4-(7-bromo-2-chloropyrido[3,2-d]pyrimidin-4-yl)morpholine (1.5 g, 0.0045 mol—Preparation 3), 3-acetamidophenylboronic acid (0.769 g, 0.0043 mol), sodium carbonate (1.2 g, 0.0113 mol), toluene (30 mL), ethanol (30 mL) and water (10 mL) were added. The reaction mixture was degassed with N2 for 5-10 minutes. To the same reaction mixture, Pd(PPh3)2Cl2 (0.159 g, 0.00022 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 to room temperature 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 column chromatography (60-120 silica gel, 60% ethyl acetate in hexane) to provide the title compound (1.3 g, 76%). 1H NMR (300 MHz, DMSO-d6): δ 10.15 (s, 1H), 9.05 (d, J=2.4 Hz, 1H), 8.18 (d, J=2.4 Hz, 1H), 8.11 (s, 1H), 7.46-7.66 (m, 3H), 4.52 (br s, 4H), 3.81 (t, J=5.1 Hz, 4H), 2.09 (s, 3H): LC-MS (ESI): Calculated mass: 383.1; Observed mass [M+H]+: 383.8. (RT=1.31 min).

Workup

  1. customThe reaction mixture was degassed with N2 for 5-10 minutes
  2. customagain degassed with N2 for 5-10 minutes
  3. temperatureThe reaction mixture was cooled to room temperature
  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 column chromatography (60-120 silica gel, 60% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-27c3d2e42fad474eb8d7fdd494bdb232
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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