cis-1-Ethoxy-2-(tri-n-butylstannyl)ethylene → tert-butyl 4-{[6-[(Z)-2-ethoxyvinyl]-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate

HRID 717882

Reaktionsgleichung

Reaktionsgleichung von HRID 717882
Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:3]=1.C([Sn](CCCC)(CCCC)/[CH:31]=[CH:32]\[O:33][CH2:34][CH3:35])CCC>C1(C)C=CC=CC=1.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>[CH2:34]([O:33]/[CH:32]=[CH:31]\[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:3]=1)[CH3:35]

Komponenten

5

Edukt 2

HCID 5706773cis-1-Ethoxy-2-(tri-n-butylstannyl)ethyleneHCID 86706861Tert-butyl 4-{[6-chloro-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate

Produkt 1

HCID 86706862tert-butyl 4-{[6-[(Z)-2-ethoxyvinyl]-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylateAusbeute 73,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A mixture of tert-butyl 4-{[6-chloro-2-(trifluoromethyl)pyrimidin-4-yl]amino}piperidine-1-carboxylate (1.0 g, 2.6 mmol, from Step 1), tributyl[(Z)-2-ethoxyvinyl]stannane (0.96 mL, 2.9 mmol, Synthonix Corp.) and tetrakis(triphenylphosphine)palladium(0) (0.15 g, 0.13 mmol, Strem) in toluene (3.0 mL) was degassed and then heated to 110° C. for 3 hours, then lowered to 90° C. overnight. The mixture was concentrated and flash chromatographed on a 120 g silica gel cartridge, eluting with a gradient from 0-20% EtOAc in hexanes to afford product as a white solid (0.8 g, 73%). 1H NMR (400 MHz, CDCl3) δ 7.08 (s, 1H), 6.58 (d, J=7.1 Hz, 1H), 5.40 (d, J=7.1 Hz, 1H), 4.98 (br s, 1H), 4.18-4.00 (m, 4H), 3.82 (br s, 1H), 2.94 (t, J=11.7 Hz, 2H), 2.12-1.95 (m, 2H), 1.52-1.31 (m, 14H). 19F NMR (376 MHz, CDCl3) δ −71.77 (s). LCMS (M+H): 417.2.

Aufarbeitung

  1. customwas degassed
  2. concentrationThe mixture was concentrated
  3. customflash chromatographed on a 120 g silica gel cartridge
  4. washeluting with a gradient from 0-20% EtOAc in hexanes

Quellen und Nachweise

ORD-Eintrag
ord-a19bb37cdef4489593fa7ef193a51f14
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193733B2

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