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2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → Isopropyl 4-(6-(6-cyano-4-methylpyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate

HRID 1811582
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1811582
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)[C:3]=1[O:21][CH3:22].[NH2:23][C:24]1[C:25]([CH3:32])=[CH:26][C:27]([C:30]#[N:31])=[N:28][CH:29]=1.C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C.O(C(C)(C)C)[Na]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].O>[C:30]([C:27]1[N:28]=[CH:29][C:24]([NH:23][C:2]2[N:7]=[CH:6][N:5]=[C:4]([O:8][CH:9]3[CH2:14][CH2:13][N:12]([C:15]([O:17][CH:18]([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]3)[C:3]=2[O:21][CH3:22])=[C:25]([CH3:32])[CH:26]=1)#[N:31]
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Komponenten

8

Edukt 4

HCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecaneHCID 51050526Isopropyl 4-[(6-chloro-5-methoxypyrimidin-4-yl)oxy]piperidine-1-carboxylateHCID 552898215-Amino-4-methylpicolinonitrileHCID 178418730sodium 2-methylpropan-2-olate

Produkt 1

HCID 11647573Isopropyl 4-(6-(6-cyano-4-methylpyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 962WaterLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a solution of isopropyl 4-(6-chloro-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate (0.3 g, 0.91 mmol) in dioxane (3 mL), were added 5-amino-4-methylpicolinonitrile (0.12 g, 0.91 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (0.031 g, 0.091 mmol), Pd(OAc)2 (0.10 g, 0.45 mmol), and NaO-t-Bu (0.21 g, 2.2 mmol) at an ambient temperature. The reaction was warmed to 75° C. and stirred for 2 hrs. After cooling to room temperature, the reaction was poured into H2O and extracted with ethyl acetate. The organic layer was dried over MgSO4 and concentrated under vacuum. The residue was purified over SiO2 to afford isopropyl 4-(6-(6-cyano-4-methylpyridin-3-ylamino)-5-methoxypyrimidin-4-yloxy)piperidine-1-carboxylate in 31% (102 mg). 1HNMR (CDCl3, 400 MHz) δ 1.21 (d, J=4.71, 6H), 1.71-1.75 (m, 2H), 1.95-2.01 (m, 2H), 2.31 (s, 3H), 2.62 (s, 3H), 3.32-3.41 (m, 2H), 3.64-3.71 (m, 2H), 4.85-4.90 (m, 1H), 5.35˜5.41 (m, 1H), 7.81 (s, 1H), 8.10 (s, 1H), 8.82 (d, J=4.71 Hz, 1H). Exact mass calculated for C21H26N6O4 426.47. found 427.51 (MH+).

Aufarbeitung

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified over SiO2

Quellen und Nachweise

ORD-Eintrag
ord-d0df0218e7c7477ab018a0891d8fa1bc
Quelldatensatz
uspto-grants-2013_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08362248B2

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