HCID 18535967, compound → HCID 11659911, compound

HRID 365381Notes

Reaction equation

HRID 365381 reaction equation
Cl.[NH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][N:7]=[C:6]2[NH:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:16][CH:15]=1>CO.C1COCC1.[Ni]>[NH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][N:7]=[C:6]2[NH:13][C:14]1[CH:15]=[CH:16][C:17]([O:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:18][CH:19]=1

Participants

4

Reactant 1

HCID 18535967HCID 18535967, compound

Product 1

HCID 11659911HCID 11659911, compoundYield 80.7%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of 6-amino-4-(4-phenoxyanilino)quinazoline hydrochloride (1.65 g, 4.2 mmol) in methanol/THF (1:1, 100 mL) was hydrogenated over Raney nickel (1 g) at 50 psi and 27° C. for 18 hours. The reaction mixture was celite filtered, and the volatiles were removed under reduced pressure. The glassy residue was partially redissolved in MeOH (25 mL), and dilute aqueous Na2CO3 solution (0.1M, 50 mL) was added with vigourous stirring. After 2 hours, the precipitate was collected by Buchner filtration, rinsed with water (50 mL), air dried, and then purified by flash chromatography on silica gel, eluting with 2.5% then 4% MeOH in CH2Cl2 to give 6-amino- 4-(4-phenoxyanilino)quinazoline (1.113 g, 80%) as a pale yellow glassy foam; mp 89-90° C., remelt 195-200° C. Calculated for C20H16N4O.0.25 H2O: C, 72.16; H, 5.00; N, 16.84%. Found: C, 72.08; H, 4.84: N, 16.81%. 1H NMR (DMSO-d6); δ9.38 (1 H, brs), 8.30 (1 H, s), 7.87 (2 H, d, J=9.0 Hz), 7.40 (1 H, d, J=8.8 Hz), 7.38 (2 H, dd, J=7.3, 8.6 Hz), 7.34 (1 H, d, J=2.4 Hz), 7.23 (1 H, dd, J=2.4, 8.9 Hz), 7.11 (1 H, t, J=7.4 Hz), 7.05 (2 H, d, J=8.8 Hz), 7.00 (2 H, d, J=7.8 Hz), 5.58 (2 H, brs). Mass spectrum (APCI) 329 (100 MH+).

Workup

  1. customthe volatiles were removed under reduced pressure
  2. dissolutionThe glassy residue was partially redissolved in MeOH (25 mL)
  3. additiondilute aqueous Na2CO3 solution (0.1M, 50 mL) was added with vigourous stirring
  4. filtrationthe precipitate was collected by Buchner filtration
  5. washrinsed with water (50 mL), air
  6. customdried
  7. custompurified by flash chromatography on silica gel
  8. washeluting with 2.5%

Sources & evidence

ORD record
ord-b38bfd63ead24a1fbad4554c83445798
Source dataset
uspto-grants-2000_10
Patent number
US06127374

Reaction notes

Loading…