Pyridine → HCID 9930632, compound

HRID 365386Notes

Reaction equation

HRID 365386 reaction equation
CCN=C=NCCCN(C)C.Cl.[NH2:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][CH:23]=1)[N:20]=[CH:19][N:18]=[C:17]2[NH:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:27][CH:26]=1.[C:39](O)(=[O:42])[CH:40]=[CH2:41].N1C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.O.CO.C(Cl)(Cl)Cl>[CH2:32]([O:31][C:28]1[CH:27]=[CH:26][C:25]([NH:24][C:17]2[C:16]3[C:21](=[CH:22][CH:23]=[C:14]([NH:13][C:39](=[O:42])[CH:40]=[CH2:41])[CH:15]=3)[N:20]=[CH:19][N:18]=2)=[CH:30][CH:29]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

9

Reactant 5

HCID 1049PyridineHCID 6581Acrylic AcidHCID 10340Sodium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 18535766HCID 18535766, compound

Product 1

HCID 9930632HCID 9930632, compoundYield 38.3%

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-benzyloxyanilino)quinazoline (342 mg, 1.0 mmol), acrylic acid (144 mg, 2.0 mmol), and pyridine (163 mg, 2.06 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 pumpkin organge solid was refluxed and sonicated in CHCl3 -acetone (1:1,40 mL), containing silica gel (5 g). The volatiles were removed under reduced pressure and the residual solid was used as the origin of a silica gel flash chromatography column, eluting with 25% acetone/CHCl3. Removal of the solvent under reduced pressure gave N-(4-[4-benzyloxyanilino]-quinazolin-6-yl)acrylamide (152 mg, 38%) as a bright yellow glass; mp 227-229° C. Calculated for C24H20N4O2C20H16N4O.0.1 HCl: C, 72.04; H, 5.06; N, 14.01%. Found: C, 71.80; H, 4.93: N, 13.80%. 1H NMR (DMSO-d6): δ10.47 (1 H, sl brs), 9.74 (1 H, sl brs), 8.76 (1 H, d, J=1.9 Hz), 8.45 (1 H, s), 7.86 (1 H, dd, J=2.0, 9.0 Hz), 7.74 (1 H, d, J=8.9 Hz), 7.66 (2 H, d, J=9.2 Hz), 7.49 (2 H, t, J=7.2 Hz), 7.41 (2 H, t, J=7.4 Hz), 7.34 (1 H, t, J=7.2 Hz), 7.04 (2 H, d, J=9.2 Hz), 6.53 (1 H, dd, J=10.1, 16.9 Hz), 6.34 (1 H, dd, J=1.9, 16.9 Hz), 5.83 (1 H, dd, J=1.9, 10.1 Hz), 5.13 (2 H, s). Mass spectrum (APCI) 397.2 (100 MH+).

Workup

  1. stirringso 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 pumpkin organge solid was refluxed
  7. customsonicated in CHCl3 -acetone (1:1,40 mL)
  8. additioncontaining silica gel (5 g)
  9. customThe volatiles were removed under reduced pressure
  10. washeluting with 25% acetone/CHCl3
  11. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-b0ed46d35ffd481baf581cc999a23c72
Source dataset
uspto-grants-2000_10
Patent number
US06127374

Reaction notes

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