Triethylamine → 4-{4-[2-(2-Hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-but-2-enoic acid ethyl ester

HRID 2079275Notes

Reaction equation

HRID 2079275 reaction equation
[CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:19]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]3)=[N:7][C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])=[N:9]2)=[CH:4][CH:3]=1.[CH2:25]([O:27][C:28](=[O:34])[CH:29]=[CH:30][C:31](O)=[O:32])[CH3:26].C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.O>[CH2:25]([O:27][C:28](=[O:34])[CH:29]=[CH:30][C:31]([N:22]1[CH2:23][CH2:24][N:19]([C:6]2[C:5]3[C:10](=[CH:11][C:2]([CH3:1])=[CH:3][CH:4]=3)[N:9]=[C:8]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[OH:18])[N:7]=2)[CH2:20][CH2:21]1)=[O:32])[CH3:26]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 413314-Ethoxy-4-oxobut-2-enoic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 1361346166-[7-methyl-4-(1-piperazinyl)-1H-quinazolin-2-ylidene]-1-cyclohexa-2,4-dienone

Product 1

HCID 1364122494-{4-[2-(2-Hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-but-2-enoic acid ethyl esterYield 91%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To 2-(7-methyl-4-piperazin-1-yl-quinazolin-2-yl)-phenol (787 mg, 2.46 mmol) in 8 mL of CH2Cl2 at room temperature was added sequentially but-2-enedioic acid monoethyl ester (531 mg, 3.69 mmol), triethylamine (686 μL, 4.92 mmol), BOP (1.63 g, 3.69 mmol). The reaction mixture was stirred for 20 min and diluted with water and CH2Cl2. The organic layer was separated and dried over Na2SO4, and the solvent was removed under reduced pressure to give an oil. The residue was subjected to purification by normal phase LC using 10-100% EtOAc-hexanes to give 4-{4-[2-(2-Hydroxy-phenyl)-7-methyl-quinazolin-4-yl]-piperazin-1-yl}-4-oxo-but-2-enoic acid ethyl ester (1.00 g, 91% yield). LC/MS: m/z 447.3 (M+H)+ at 2.93 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. customthe solvent was removed under reduced pressure
  4. customto give an oil
  5. customThe residue was subjected to purification by normal phase LC

Sources & evidence

ORD record
ord-46f42896e15c4c71bbde1df38db230e8
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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