1,4-Dioxane → HCID 86710183, compound

HRID 2284418Notes

Reaction equation

HRID 2284418 reaction equation
Cl[C:2]1[N:11]=[C:10]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:9]2[C:4](=[CH:5][C:6]([C:18]3[CH:19]=[C:20]([CH:22]=[CH:23][CH:24]=3)[NH2:21])=[CH:7][CH:8]=2)[N:3]=1.[C:25]([O:29][C:30]([NH:32][C:33]1[N:38]=[CH:37][C:36](B(O)O)=[CH:35][N:34]=1)=[O:31])([CH3:28])([CH3:27])[CH3:26].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:21][C:20]1[CH:19]=[C:18]([C:6]2[CH:5]=[C:4]3[C:9]([C:10]([N:12]4[CH2:17][CH2:16][O:15][CH2:14][CH2:13]4)=[N:11][C:2]([C:36]4[CH:37]=[N:38][C:33]([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:27])([CH3:26])[CH3:28])=[N:34][CH:35]=4)=[N:3]3)=[CH:8][CH:7]=2)[CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 45489688{2-[(tert-Butoxycarbonyl)amino]pyrimidin-5-yl}boronic acidHCID 86710184HCID 86710184, compound

Product 1

HCID 86710183HCID 86710183, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

In 50 mL round bottom flask, 3-(2-chloro-4-morpholinoquinazolin-7-yl)aniline (0.6 g, 0.0018 mol), (2-((tert-butoxycarbonyl)amino)pyrimidin-5-yl)boronic acid (0.506 g, 0.0022), potassium phosphate (1.08 g, 0.0054 mol), 1,4-dioxane (20 mL) and water (5 mL) were added. The reaction mixture was degassed with N2 for 5-10 minutes. To the same reaction mixture, Pd (PPh3)4 (0.098 g, 0.00009 mol) was added and degassed with N2 for 5-10 minutes. The reaction mixture was stirred at 95° C. for 2 hours. The reaction mass was cooled to room temperature and water was added. The crude product was extracted with ethyl acetate (3×100 mL). The combined organic layer was washed with brine, dried over sodium sulfate and evaporated under reduced pressure to provide the crude product. The crude product was purified by flash column chromatography (2% methanol in chloroform) to provide the title compound (0.3 g, 34%). 1H NMR (400 MHz, DMSO-d6): δ 10.40 (s, 1H), 9.49 (s, 2H), 8.12 (d, J=8.8 Hz, 1H), 8.01 (d, J=1.6 Hz, 1H), 7.75 (dd, J′=8.8 Hz, J″=1.6 Hz, 1H), 7.20 (t, J=7.6 Hz, 1H), 7.04 (br s, 1H), 6.98 (d, J=7.6 Hz, 1H), 6.66 (d, J=8.4 Hz, 1H), 5.29 (s, 2H), 3.90 (d, J=4.4 Hz, 4H), 3.84 (d, J=4.0 Hz, 4H), 1.49 (s, 9H): LC-MS (ESI): Calculated mass. 499.2, Observed mass [M+H]+: 500.4. (RT=0.78 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 mass was cooled to room temperature
  4. additionwater was added
  5. extractionThe crude product was extracted with ethyl acetate (3×100 mL)
  6. washThe combined organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. customevaporated under reduced pressure
  9. customto provide the crude product
  10. customThe crude product was purified by flash column chromatography (2% methanol in chloroform)

Sources & evidence

ORD record
ord-a249b21e654b44b3854d3392f47ca5af
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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