2,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecane → Hydrochloric Acid

HRID 1811568

Reaktionsgleichung

Reaktionsgleichung von HRID 1811568
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([Cl:22])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[CH3:23][S:24]([C:27]1[N:32]=[CH:31][C:30]([NH2:33])=[C:29]([CH3:34])[CH:28]=1)(=[O:26])=[O:25].C(N1CCN2CCN(CC(C)C)P1N(CC(C)C)CC2)C(C)C.CC([O-])(C)C.[Na+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([NH:33][C:30]3[CH:31]=[N:32][C:27]([S:24]([CH3:23])(=[O:26])=[O:25])=[CH:28][C:29]=3[CH3:34])[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].[ClH:22]

Komponenten

8

Edukt 4

HCID 45712432,8,9-Triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo(3.3.3)undecaneHCID 23676156Sodium t-butoxideHCID 51050526Isopropyl 4-[(6-chloro-5-methoxypyrimidin-4-yl)oxy]piperidine-1-carboxylateHCID 586715824-Methyl-6-(methylsulfonyl)pyridin-3-amine

Produkt 2

HCID 313Hydrochloric AcidHCID 115838194-[6-(6-Methanesulfonyl-4-methyl-pyridin-3-ylamino)-5-methoxy-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 4-(6-chloro-5-methoxy-pyrimidin-4-yloxy)-piperidine-1-carboxylic acid isopropyl ester (570 mg, 1.73 mmol), 6-methanesulfonyl-4-methyl-pyridin-3-ylamine (272 mg, 1.46 mmol), palladium acetate (27.3 mg, 0.122 mmol), 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phospha-bicyclo[3.3.3]undecane (87 μl, 0.245 mmol), and sodium 2-methylpropan-2-olate (249 mg, 2.59 mmol) in 4.5 mL dioxane was heated under microwave irradiation at 120° C. After 4 h, mixture was purified by HPLC; fractions containing pure product were collected and concentrated. Residue was treated with 4M HCl in dioxane, concentrated, and dried under high vacuum to give 4-[6-(6-methanesulfonyl-4-methyl-pyridin-3-ylamino)-5-methoxy-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester as a white solid (HCl salt, 261 mg, 29%). 1HNMR (MeOH-d4, 400 MHz) δ 1.23-1.24 (d, J=6.2 Hz, 6H), 1.75-1.81 (m, 2H), 1.97-2.04 (m, 2H), 2.40 (s, 3H), 3.17 (s, 3H), 3.39-3.46 (m, 2H), 3.71-3.77 (m, 2H), 3.92 (s, 3H), 4.82-4.88 (m, 1H), 5.35-5.40 (m, 1H), 7.99 (s, 1H), 7.99 (s, 1H), 8.96 (s, 1H). Exact mass calculated for C21H29N5O6S 479.18 found 480.4 (MH+).

Aufarbeitung

  1. custommixture was purified by HPLC
  2. additionfractions containing pure product
  3. customwere collected
  4. concentrationconcentrated
  5. additionResidue was treated with 4M HCl in dioxane
  6. concentrationconcentrated
  7. customdried under high vacuum

Quellen und Nachweise

ORD-Eintrag
ord-9434f1c03bf643cc926a658565da2925
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362248B2

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