2-(Pyrimidin-2-yl)but-3-yn-2-ol → 1-(2-amino-6-chloropyrimidin-4-yl)-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]-1H-indazole-3-carboxylic acid

HRID 1398622

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14](I)[CH:15]=3)[C:10]([C:18]([OH:20])=[O:19])=[N:9]2)[CH:5]=[C:4]([Cl:21])[N:3]=1.[N:22]1[CH:27]=[CH:26][CH:25]=[N:24][C:23]=1[C:28]([OH:32])([C:30]#[CH:31])[CH3:29]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(N(CC)CC)C>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:31]#[C:30][C:28]([OH:32])([C:23]4[N:24]=[CH:25][CH:26]=[CH:27][N:22]=4)[CH3:29])[CH:15]=3)[C:10]([C:18]([OH:20])=[O:19])=[N:9]2)[CH:5]=[C:4]([Cl:21])[N:3]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of 1-(2-amino-6-chloropyrimidin-4-yl)-6-iodo-1H-indazole-3-carboxylic acid (750 mg, 1.81 mmol) in 1:1 triethylamine/dry THF (12 mL) was introduced bis(triphenylphosphine)palladium(II) chloride (127 mg, 0.18 mmol), copper(I) iodide (34 mg, 0.18 mmol) and 2-(pyrimidin-2-yl)but-3-yn-2-ol (535 mg, 3.61 mmol). The reaction mixture was warmed to 55° C. for 1 hr. After cooling to RT, the reaction mixture was concentrated in vacuo to furnish the crude title compound: 1H NMR (500 MHz, DMSO) delta 1.92 (3H, s), 6.26 (1H, s), 7.09 (1H, s), 7.39 (1H, d, J=8.2 Hz), 7.51 (1H, t, J=4.9 Hz), 8.23 (1H, d, J=8.6 Hz), 8.82 (1H, s), 8.90 (2H, d, J=4.9 Hz); LC-MS: m/z=+436.05/437.70 (M+H)+. This compound, with LC-MS purity=91% UV, was used in the next step without further purification.

Workup

temperatureAfter cooling to RT
concentrationthe reaction mixture was concentrated in vacuo

Sources & evidence

ORD record: ord-4d54464231884fd0ab3c176691270a30
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901313B2

Linked notes

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