Water → Methyl 2-(2-((tert-butoxycarbonylamino)methyl)piperidin-1-yl)-4-cyano-6-(m-tolylamino)pyrimidine-5-carboxylate

HRID 516010Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 516010
[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][N:11]1[C:16]1[N:21]=[C:20](Cl)[C:19]([C:23]([O:25][CH3:26])=[O:24])=[C:18]([NH:27][C:28]2[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.[CH3:36][N:37](C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C-]#N.[Zn+2].[C-]#N>[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][N:11]1[C:16]1[N:21]=[C:20]([C:36]#[N:37])[C:19]([C:23]([O:25][CH3:26])=[O:24])=[C:18]([NH:27][C:28]2[CH:29]=[C:30]([CH3:34])[CH:31]=[CH:32][CH:33]=2)[N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 962WaterHCID 6228DimethylformamideHCID 86654715Methyl 2-(2-((tert-butoxycarbonylamino)methyl)piperidin-1-yl)-4-chloro-6-(m-tolylamino)pyrimidine-5-carboxylate

Produkt 1

HCID 67238205Methyl 2-(2-((tert-butoxycarbonylamino)methyl)piperidin-1-yl)-4-cyano-6-(m-tolylamino)pyrimidine-5-carboxylateAusbeute 80 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of methyl 2-(2-((tert-butoxycarbonylamino)methyl)piperidin-1-yl)-4-chloro-6-(m-tolylamino)pyrimidine-5-carboxylate (399.7 mg, 0.816 mmol), tetrakis(triphenylphosphine)palladium(0) (96.3 mg, 0.083 mmol), and zinc cyanide (53.2 mg, 0.453 mmol) in DMF (5 mL) was stirred at 120° C. for 1 h under microwave irradiation. Water (50 mL) was added and the mixture was extracted with EtOAc (2×100 mL). The organic layers were washed with saturated aq NaHCO3 (50 mL), water (50 mL), and brine (50 mL), were dried over anhydrous Na2SO4, and then filtered (DM1020). The filtrate was concentrated under reduced pressure and was purified by column chromatography (SiO2, hexanes/EtOAc=4/1) to give the title compound as a colorless oil (315.0 mg, 80%). 1H NMR (500 MHz, CDCl3) δ ppm 1.34-1.77 (m, 15H), 2.36-2.39 (m, 3H), 3.00-3.21 (m, 2H), 3.49-3.69 (m, 1H), 3.97 (s, 3H), 4.49-5.10 (m, 3H), 6.96-7.02 (m, 1H), 7.24-7.41 (m, 3H), 10.14-10.45 (m, 1H). [M+H] calc'd for C25H33N6O4, 481; found, 481.

Aufarbeitung

  1. extractionthe mixture was extracted with EtOAc (2×100 mL)
  2. washThe organic layers were washed with saturated aq NaHCO3 (50 mL), water (50 mL), and brine (50 mL)
  3. dry with materialwere dried over anhydrous Na2SO4
  4. filtrationfiltered (DM1020)
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customwas purified by column chromatography (SiO2, hexanes/EtOAc=4/1)

Quellen und Nachweise

ORD-Eintrag
ord-b61146958e3c46b0bb4cbd4f7e781bfe
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09108970B2

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