3-Amino-6-chloro-2-picoline → 4-[6-(6-Chloro-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic Acid Isopropyl Ester

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Reaktionsgleichung

[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18](Cl)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].CC(C)([O-])C.[Na+].[Cl:28][C:29]1[N:34]=[C:33]([CH3:35])[C:32]([NH2:36])=[CH:31][CH:30]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C2C=CC=CC=2)C=CC=C(P(C(C)(C)C)C(C)(C)C)C=1>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([CH3:20])=[C:18]([NH:36][C:32]3[C:33]([CH3:35])=[N:34][C:29]([Cl:28])=[CH:30][CH:31]=3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Komponenten

Reaktionsbedingungen

Temperatur: 120 °C

Versuchsvorschrift

A mixture of 4-(6-chloro-5-methyl-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (1.546 g, 4.93 mmol), palladium acetate (110 mg, 0.49 mmol), biphenyl-3-yl-di-tert-butyl-phosphane (18.5 mg, 0.062 mmol), sodium tert-butoxide (1.20 g, 12.5 mmol), and 6-chloro-2-methyl-pyridin-3-ylamine (709 mg, 4.97 mmol) in 15 mL dioxane was heated in microwave for 2 hour at 120° C. Solids were filtered off and mixture was purified to give Compound A90 as a tanned solid (640 mg, 31%). 1H NMR (CDCl3, 400 MHz) δ 1.11-1.12 (d, 6H), 1.52-1.62 (m, 2H), 1.81-1.89 (m, 2H), 1.98 (s, 3H), 2.23 (m, 3H), 3.21-3.30 (m, 2H), 3.59-3.70 (m, 3H), 5.14-5.17 (m, 1H), 6.83-6.91 (m, 1H), 7.14-7.16 (d, 1H), 7.55-7.57 (d, 1H), 7.87 (s, 1H). Exact mass calculated for C20H26ClN5O3 419.17, found 419.9 (MH+).

Aufarbeitung

filtrationSolids were filtered off
custommixture was purified

Quellen und Nachweise

ORD-Eintrag: ord-b3865050b251440a858e5b0f4b29b523
Quelldatensatz: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US08546429B2

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