Dimethylformamide → HCID 73056227, compound

HRID 2284402Notes

Reaction equation

HRID 2284402 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:19]3[CH:24]=[CH:23][CH:22]=[C:21]([S:25]([CH3:28])(=[O:27])=[O:26])[CH:20]=3)=[C:7](F)[CH:8]=2)[N:3]=1.[NH2:29][C:30]1[N:35]=[CH:34][C:33](B(O)O)=[CH:32][N:31]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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>[CH3:28][S:25]([C:21]1[CH:20]=[C:19]([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:33]4[CH:32]=[N:31][C:30]([NH2:29])=[N:35][CH:34]=4)=[N:3]3)=[CH:8][CH:7]=2)[CH:24]=[CH:23][CH:22]=1)(=[O:27])=[O:26]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 17750211(2-Aminopyrimidin-5-yl)boronic acidHCID 86710172HCID 86710172, compound

Product 1

HCID 73056227HCID 73056227, compoundYield 72.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 50 mL round bottom flask, 4-(2-chloro-6-fluoro-7-(3-(methylsulfonyl)phenyl)quinazolin-4-yl)morpholine (0.06 g, 0.00015 mol), (2-aminopyrimidin-5-yl)boronic acid (0.03 g, 0.00023 mol), cesium carbonate (0.097 g, 0.0003 mol), DMF (5 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 (0.005 g, 0.0000075 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 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, 0-5% methanol in chloroform) to provide the desired product (0.05 g, 7%). 1H NMR (400 MHz, DMSO-d6): δ 9.22 (s, 2H), 8.36 (s, 1H), 8.25 (s, 1H), 8.22 (d, J=2.0 Hz, 1H), 8.15 (d, J=8.8 Hz, 1H), 8.01 (d, J=8.0 Hz, 1H), 7.87-7.80 (m, 2H), 7.21 (s, 2H), 3.85 (s, 8H); 1H NMR (400 MHz, DMSO-d6+D2O): δ 9.12 (s, 2H), 8.20 (s, 1H), 8.14-8.06 (m, 3H), 7.95 (d, J=7.6 Hz, 1H), 7.79 (t, J=7.2 Hz, 2H), 3.83-3.77 (m, 8H), 3.21 (s, 3H). LC-MS (ESI): Calculated mass: 462.1; Observed mass [M+H]+: 463.1 (RT=0.23 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. 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, 0-5% methanol in chloroform)

Sources & evidence

ORD record
ord-12719264d3644b6fa4748fa018c6abd9
Source dataset
uspto-grants-2015_09
Patent number
US09145411B2

Reaction notes

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