Triethylamine → 1-(4-Amino-quinazolin-7-ylmethyl)-4-(3-biphenyl-2-yl-prop-2-ynyl)-piperazin-2-one

HRID 1432964Notes

Reaction equation

[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([CH2:19][C:20]#[CH:21])[CH2:15][C:14]3=[O:22])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.Br[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CCN(CC)CC>CN(C=O)C.[Cu]I>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([CH2:19][C:20]#[C:21][C:35]4[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=4[C:25]4[CH:24]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:15][C:14]3=[O:22])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A solution containing 1-(4-amino-quinazolin-7-ylmethyl)-4-prop-2-ynyl-piperazin-2-one (50 mg, 0.17 mmol), EXAMPLE 283, 2-bromobiphenyl (44 mg, 0.19 mmol), Et3N (69 mg, 0.68 mmol), (Ph3P)4PdCl2 (6 mg, 0.008 mmol), and CuI (1 mg, 0.005 mmol) in anhydrous DMF (2 mL) is warmed at 80° C. for 1 hours. The reaction mixture is cooled to 50° C. and the solvent is removed over 16 h under a stream of nitrogen. The crude residue is purified by flash silica gel chromatography (CH2Cl2 to 10% MeOH CH2Cl2) to afford a colorless gum which is triturated with ethyl alcohol to provide 4 mg (5%) of the title compound as a white solid. 1H NMR (300 MHz, d6-DMSO) δ3.03 (s, 2H), 3.14 (m, 2H), 3.31 (m, 2H), 3.50 (s, 2H), 7.21-7.55 (m, 11H), 7.76 (br s, 2H), 8.18 (d, J=8.6 Hz, 1H), 8.36 (s, 1H) ppm; MS (ion spray): m/z 448 (M+H).

Workup

temperatureThe reaction mixture is cooled to 50° C.
customthe solvent is removed over 16 h under a stream of nitrogen
customThe crude residue is purified by flash silica gel chromatography (CH2Cl2 to 10% MeOH CH2Cl2)
customto afford a colorless gum which
customis triturated with ethyl alcohol

Sources & evidence

ORD record: ord-2c5a2fb060a44bd2b87bd9edb141a1f0
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612075B2

Reaction notes

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