Triethylamine → (S)-1-(3-(4-amino-3-((3-methoxyphenyl)ethynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one

HRID 516190

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:12]3[CH2:16][CH2:15][N:14]([C:17](=[O:24])[CH:18]=[CH:19][CH2:20][N:21]([CH3:23])[CH3:22])[CH2:13]3)[N:9]=[C:10](I)[C:3]=12.[C:25]([C:27]1[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=1)#[CH:26].C(N(CC)CC)C>C1COCC1.C(OCC)(=O)C.CO.[Cu]I>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:12]3[CH2:16][CH2:15][N:14]([C:17](=[O:24])[CH:18]=[CH:19][CH2:20][N:21]([CH3:23])[CH3:22])[CH2:13]3)[N:9]=[C:10]([C:26]#[C:25][C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH3:34])[CH:28]=3)[C:3]=12

Participants

Conditions

Temperature: 80 °C

Procedure

PdCl2(dppf)CH2Cl2 (1.3 mg) was added to a mixture of (S)-1-(3-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one (8.0 mg) obtained in Step 1, 1-ethynyl-3-methoxybenzene (4.0 mg), copper (I) iodide (0.6 mg), and triethylamine (8.6 μl) in THF (1.0 ml). After nitrogen purging, the resulting mixture was stirred at 80° C. overnight. The reaction mixture was diluted with ethyl acetate and methanol. The resulting diluted solution was treated with basic silica gel, and then concentrated. The resulting residue was purified by reversed-phase HPLC purification (water/acetonitrile (0.1% formic acid)) to obtain the title compound as a colorless, amorphous substance (1.4 mg). Table 2 shows the physical properties thereof.

Workup

additionThe resulting diluted solution was treated with basic silica gel
concentrationconcentrated
customThe resulting residue was purified by reversed-phase HPLC purification (water/acetonitrile (0.1% formic acid))

Sources & evidence

ORD record: ord-9fed6ca33cbe4b04a77c6b1b647a1dad
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09108973B2

Linked notes

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