1-(2-Aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid → 1-(2-Aminopyrimidin-4-yl)-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]indazole-3-carboxylic acid

HRID 1398591

Reaktionsgleichung

Reaktionsgleichung von HRID 1398591
[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]=[CH:4][N:3]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[N:23][C:22]=1[C:27]([OH:31])([C:29]#[CH:30])[CH3:28]>C(N(CC)CC)C.C1COCC1.[Cu]I.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>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:30]#[C:29][C:27]([OH:31])([C:22]4[N:23]=[CH:24][CH:25]=[CH:26][N:21]=4)[CH3:28])[CH:15]=3)[C:10]([C:18]([OH:20])=[O:19])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Komponenten

7

Edukt 2

HCID 681816001-(2-Aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acidHCID 866695882-(Pyrimidin-2-yl)but-3-yn-2-ol

Produkt 1

HCID 681816771-(2-Aminopyrimidin-4-yl)-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]indazole-3-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
55 °C

Versuchsvorschrift

To a pressure tube containing 1-(2-aminopyrimidin-4-yl)-6-iodoindazole-3-carboxylic acid (550 mg, 1.44 mmol), copper(I) iodide (27.48 mg, 0.14 mmol), bis(triphenylphosphine)palladium(II) chloride (101.29 mg, 0.14 mmol) in triethylamine (4 mL) and THF (4 mL), was added 2-(pyrimidin-2-yl)but-3-yn-2-ol (427.62 mg, 2.89 mmol). The reaction was sealed and stirred at 55° C. for 1 hr. The reaction mixture was concentrated in vacuo and the crude product was purified by column chromatography (Biotage, 5-10% methanol in DCM followed by 10-20% [7M NH3 in methanol] in DCM) to give the title intermediate as an orange/brown oil: 1H NMR (250 MHz, DMSO) delta 1.92 (3H, s), 6.27 (1H, s), 6.98 (3H, s), 7.09 (1H, d, J=5.5 Hz), 7.26 (1H, d, J=9.5 Hz), 7.50 (1H, t, J=4.9 Hz), 8.20-8.41 (3H, m), 8.73-9.02 (2H, m); LC-MS: m/z=+402.00 (M+H)+.

Aufarbeitung

  1. customThe reaction was sealed
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe crude product was purified by column chromatography (Biotage, 5-10% methanol in DCM followed by 10-20% [7M NH3 in methanol] in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-a8dd9cf3d93842f8b0c78402c45282fe
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08901313B2

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