HCID 18535765, compound → HCID 18535766, compound

HRID 365385Notes

Reaction equation

HRID 365385 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][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=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][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[CH:18][CH:19]=1

Participants

4

Reactant 1

HCID 18535765HCID 18535765, compound

Product 1

HCID 18535766HCID 18535766, compoundYield 83.3%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

A solution of 6-amino-4-(4-benzyloxyanilino)quinazoline hydrochloride (1.46 g, 3.57 mmol) in methanol/THF (1:1, 100 mL) was hydrogenated over Raney nickel (1 g) at 51.5 psi and 23° C. for 18 hours. The reaction mixture was celite filtered, and the volatiles were removed under reduced pressure. The crystalline brown residue was partially redissolved in MeOH (25 mL), and dilute aqueous Na2CO3 solution (0.1 M, 50 mL) was added with vigourous stirring. After 2 hours, the precipitate was collected by Buchner filtration, rinsed with water (50 mL), dried in a vacuum oven at 60° C., and then purified by flash chromatography on silica gel, eluting with CHCl3 then 4% MeOH in CHCl3 to give 6-amino-4-(4-benzyloxyanilino)quinazoline (1.018 g, 80%) as a cream powder; mp 173-175° C., remelt 240-245° C. Calculated for C20H16N4O.0.67 H2O: C, 71.16; H, 5.50; N, 15.81%. Found: C, 71.03; H, 5.38; N, 13.48%. 1H NMR (DMSO-d6); δ9.25 (1 H, brs), 8.25 (1 H,s), 7.70 (2 H, d, J=9.0 Hz), 7.52-7.47 (3 H, m), 7.41 (2 H, t, J=7.5 Hz), 7.38-7.35 (2 H, m), 7.02 (2 H, d, J=9.0 Hz), 5.54 (2 H, brs), 5.11 (2 H, s). Mass spectrum (APCI) 343 (100 MH+).

Workup

  1. customthe volatiles were removed under reduced pressure
  2. dissolutionThe crystalline brown residue was partially redissolved in MeOH (25 mL)
  3. additiondilute aqueous Na2CO3 solution (0.1 M, 50 mL) was added with vigourous stirring
  4. filtrationthe precipitate was collected by Buchner filtration
  5. washrinsed with water (50 mL)
  6. customdried in a vacuum oven at 60° C.
  7. custompurified by flash chromatography on silica gel
  8. washeluting with CHCl3

Sources & evidence

ORD record
ord-23e4f67f5f7144ca99541806120a092a
Source dataset
uspto-grants-2000_10
Patent number
US06127374

Reaction notes

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