Water → HCID 67298523, compound

HRID 1520312Notes

Reaction equation

HRID 1520312 reaction equation
[H-].[Na+].[C:3]([NH2:12])(=[O:11])[C:4]1[C:5](=[CH:7][CH:8]=[CH:9][CH:10]=1)[OH:6].Cl[C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([O:24][CH2:25][CH3:26])[CH:22]=2)[N:17]=[C:16]([C:27]2[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=2)[N:15]=1.O>CN(C=O)C>[CH2:25]([O:24][C:21]1[CH:22]=[C:23]2[C:18](=[CH:19][CH:20]=1)[N:17]=[C:16]([C:27]1[CH:28]=[N:29][CH:30]=[CH:31][CH:32]=1)[N:15]=[C:14]2[O:6][C:5]1[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=1[C:3]([NH2:12])=[O:11])[CH3:26]

Participants

6

Reactant 4

HCID 962WaterHCID 5147SalicylamideHCID 24758Sodium hydrideHCID 86677069HCID 86677069, compound

Product 1

HCID 67298523HCID 67298523, compoundYield 10.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(The method G8 is representative of method G6, G7, G9, G10 and G11. These six methods can be implemented in a similar way except for substitution of the appropriate base, solvent and temperature) To a 2.5 dram reaction vial was first added sodium hydride 60% (0.028 g, 0.700 mmol) and salicylamide (0.072 g, 0.525 mmol) in DMF (2 mL). The mixture was allowed to stir at room temperature for 1 h. Then, 4-chloro-6-ethoxy-2-(pyridin-3-yl)quinazoline (0.100 g, 0.350 mmol) was added to the mixture, and the reaction was allowed to proceed at room temperature overnight. LC-MS analysis of the crude mixture showed about 85% of product formed and 10% remaining starting material. Water (30 mL) was added to the mixture, and the product was extracted with chloroform (3×15 mL). The combined organic layers were dried (Na2SO4), filtered, and concentrated. The crude product was purified via ISCO (silica gel, 97.5:2.5 CH2Cl2/MeOH; 12 g column) to afford 13.9 mg of the desired product as a white solid (10.3%) LCMS m/z=387 (M+1) (Method C) (retention time=2.05 min). 1H NMR (300 MHz, DMSO) δ 11.47 (s, 2H), 9.39 (s, 1H), 8.66 (d, J=2.8 Hz, 1H), 8.56-8.47 (m, 1H), 8.01-7.90 (m, 2H), 7.69-7.55 (m, 2H), 7.55-7.40 (m, 2H), 7.05 (t, J=7.5 Hz, 1H), 6.97 (d, J=8.2 Hz, 1H), 4.23 (q, J=6.9 Hz, 2H), 1.44 (t, J=6.9 Hz, 3H).

Workup

  1. customTo a 2.5 dram reaction
  2. waitto proceed at room temperature overnight
  3. customformed
  4. extractionthe product was extracted with chloroform (3×15 mL)
  5. dry with materialThe combined organic layers were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified via ISCO (silica gel, 97.5:2.5 CH2Cl2/MeOH; 12 g column)

Sources & evidence

ORD record
ord-82f2f961e70e4e2da1517d2754c8ee85
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

Loading…