Pyridine → HCID 10547930, compound

HRID 365382Notes

Reaction equation

HRID 365382 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]=[C:5]2[NH:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:15][CH:14]=1.[C:26](O)(=[O:29])[CH:27]=[CH2:28].N1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.O.CO.C(Cl)(Cl)Cl>[O:19]([C:16]1[CH:15]=[CH:14][C:13]([NH:12][C:5]2[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:26](=[O:29])[CH:27]=[CH2:28])[CH:3]=3)[N:8]=[CH:7][N:6]=2)=[CH:18][CH:17]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 6581Acrylic AcidHCID 10340Sodium CarbonateHCID 11659911HCID 11659911, compound

Product 1

HCID 10547930HCID 10547930, compoundYield 42.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
0 °C

Procedure

3,N-(N,N-Dimethylaminopropyl)-1,N-ethylcarbodiimide hydrochloride (EDAC.HCl) (385 mg, 2.0 mmol) was added in one portion to a solution of 6-amino-4-(4-phenoxyanilino)quinazoline (328 mg, 1.0 mmol), acrylic acid (148 mg, 2.04 mmol), and pyridine (165 mg, 2.1 mmol) in THF (10 mL) stirred under nitrogen at 0° C. After 4 hours at 0° C. tlc (10% MeOH/CHCl3) showed considerable SM, so the reaction mixture was stirred at 25° C. for 2 hours. The mixture was recooled to 0° C., and water (2 mL) was added dropwise. This solution was poured onto rapidly stirred ice-water (40 mL), the pH was raised to 7 with saturated Na2CO3 solution, and the very fine ppt was allowed to settle, collected by Buchner filtration, rinsed with water (2×10 mL), and dried in a vacuum oven at 65° C. for 4 hours. The pale yellow solid was refluxed and sonicated in EtOAc (10 mL), filtered, and the filtrate was eluted through a small silica gel plug with EtOAc. The combined washings were stripped rigourously at 25° C. under vacuum to give N-(4-[4-phenoxyanilino]quinazolin-6yl)acrylamide (162 mg, 41%) as a pale yellow glass; mp 185-191° C. Calculated for C23H18N4O2C20H16N4O.0.25 HCl.0.06 C4H8O2 : C, 70.34; H, 4.76; N, 14.12%. Found: C, 70.42; H, 4.80: N, 13.90%. 1H NMR (DMSO-d6): δ10.50 (1 H, sl brs), 9.86 (1 H, sl brs), 8.80 (1 H, d, J=2.0 Hz), 8.50 (1 H, s), 7.89 (1 H, dd, J=2.2, 9.0 Hz), 7.81 (2 H, d, J=8.9 Hz), 7.77 (1 H, d, J=9.0 Hz), 7.39 (2 H, dd, J=7.6, 8.6 Hz), 7.12 (1 H, t, J=7.4 Hz), 7.06 (2 H, d, J=8.8 Hz), 7.02 (2 H, d, J=7.8 Hz), 6.53 (1 H, dd, J=1.01, 17.0 Hz), 6.34 (1 H, dd, J=1.8, 17.0 Hz), 5.84 (1 H, dd, J=1.8 10.1 Hz). Mass spectrum (APCI) 383.1 (100 MH+).

Workup

  1. stirringSM, so the reaction mixture was stirred at 25° C. for 2 hours
  2. customwas recooled to 0° C.
  3. filtrationcollected by Buchner filtration
  4. washrinsed with water (2×10 mL)
  5. customdried in a vacuum oven at 65° C. for 4 hours
  6. temperatureThe pale yellow solid was refluxed
  7. customsonicated in EtOAc (10 mL)
  8. filtrationfiltered
  9. washthe filtrate was eluted through a small silica gel plug with EtOAc
  10. customwere stripped rigourously at 25° C. under vacuum

Sources & evidence

ORD record
ord-6a4014d7397d4c3382db41ba8e99688a
Source dataset
uspto-grants-2000_10
Patent number
US06127374

Reaction notes

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