Sodium Bicarbonate → Tert-butyl 4-(6-(5-(phenylsulfonamido)-pyridine-3-yl)pyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate

HRID 1485550Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1485550
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([O:12][CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]3)[C:10]=2[N:11]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([NH:40][S:41]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)(=[O:43])=[O:42])[CH:37]=[N:38][CH:39]=2)O1.C(=O)(O)[O-].[Na+]>O1CCOCC1>[C:44]1([S:41]([NH:40][C:36]2[CH:35]=[C:34]([C:2]3[CH:3]=[CH:4][C:5]4[N:6]=[CH:7][N:8]=[C:9]([O:12][CH:13]5[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]5)[C:10]=4[N:11]=3)[CH:39]=[N:38][CH:37]=2)(=[O:43])=[O:42])[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

Komponenten

5

Edukt 3

HCID 516892Sodium BicarbonateHCID 52936632N-[5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]benzenesulfonamide2×HCID 86671067Tert-butyl 4-(6-chloropyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate

Produkt 1

HCID 66558111Tert-butyl 4-(6-(5-(phenylsulfonamido)-pyridine-3-yl)pyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylateAusbeute 32,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A mixture of tert-butyl 4-(6-chloropyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate (0.3 g, 0.822 mmol), N-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzene-sulfonamide (Intermediate 2) (0.355 g, 0.987 mmol), PdCl2(dppf)-CH2Cl2Adduct (0.067 g, 0.082 mmol) and 1N aq. sodium bicarbonate (1.64 ml, 1.64 mmol) in dioxane (4.11 ml) was subjected to microwave irradiation for 30 min at 120° C., and cooled to room temperature. The reaction mixture was filtered through a Celite pad and washed with EtOAc. The filtrate was diluted water and extracted with EtOAc. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to give tert-butyl 4-(6-(5-(phenylsulfonamido)-pyridine-3-yl)pyrido[3,2-d]pyrimidin-4-yloxy)piperidine-1-carboxylate (0.15 g, 32%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.49 (9H, s), 1.95-2.05 (2H, m), 2.14-2.18 (2H, m), 3.36-3.43 (2H, m), 3.89-3.95 (2H, m), 5.63-5.37 (1H, m), 7.46-7.52 (2H, m), 7.56-7.60 (1H, m), 7.85 (1H, d, J=7.2 Hz), 8.21 (1H, d, J=8.8 Hz), 8.34 (1H, s), 8.37 (1H, d, J=2.4 Hz), 8.41 (1H, d, J=2.0 Hz), 8.83 (1H, s), 9.14 (1H, d, J=1.6 Hz).

Aufarbeitung

  1. customirradiation for 30 min at 120° C.
  2. filtrationThe reaction mixture was filtered through a Celite pad
  3. washwashed with EtOAc
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)

Quellen und Nachweise

ORD-Eintrag
ord-4a7a7cf76b8f42268489da550af14610
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09422298B2

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