Cesium carbonate → methyl 6-(5-methylpyrazin-2-ylamino)-4-(1-Boc-piperidin-4-ylmethylamino)nicotinate

HRID 556806Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 556806
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][NH:15][C:16]2[C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][N:19]=[C:18](Cl)[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][C:28]1[N:29]=[CH:30][C:31]([NH2:34])=[N:32][CH:33]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>>[CH3:27][C:28]1[N:29]=[CH:30][C:31]([NH:34][C:18]2[CH:17]=[C:16]([NH:15][CH2:14][CH:11]3[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:9][CH2:10]3)[C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][N:19]=2)=[N:32][CH:33]=1

Komponenten

5

Edukt 4

HCID 10796Cesium carbonateHCID 3132155-Methylpyrazin-2-amineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59613527Methyl 4-((1-(tert-butoxycarbonyl)piperidin-4-yl)methylamino)-6-chloronicotinate

Produkt 1

HCID 66745630methyl 6-(5-methylpyrazin-2-ylamino)-4-(1-Boc-piperidin-4-ylmethylamino)nicotinateAusbeute 33,3 %

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

Methyl 4-((1-(tert-butoxycarbonyl)piperidin-4-yl)methylamino)-6-chloronicotinate (90 mg, 0.23 mmol), 5-methylpyrazin-2-amine (38 mg, 0.35 mmol, as described in Itoh et al., 2002), cesium carbonate (153 mg, 0.47 mmol), 4,5-bis(diphenyl phosphino)-9,9-dimethylxanthene (11 mg, 8 mol %), and tris(dibenzylidene acetone)dipalladium chloroform complex (10 mg, 4 mol %) were added to an oven-dried microwave reactor vial (2 mL) which was capped and flushed with nitrogen. Anhydrous toluene (1.35 mL) was added and nitrogen was bubbled through the stirred solution for 10 minutes. The mixture was heated at 130° C. for 30 minutes by microwave irradiation. The solution was cooled, diluted with dichloromethane-methanol and adsorbed onto a 2 g (solute SCX-II column. The resin was washed with methanol, then with 2M ammonia in methanol. The basic fractions were concentrated and the residue was purified by preparative TLC, eluting with 10% methanol-dichloromethane) to give methyl 6-(5-methylpyrazin-2-ylamino)-4-(1-Boc-piperidin-4-ylmethylamino)nicotinate (35 mg) as a light green powder.

Aufarbeitung

  1. customwas capped
  2. customflushed with nitrogen
  3. additionAnhydrous toluene (1.35 mL) was added
  4. customnitrogen was bubbled through the stirred solution for 10 minutes
  5. temperatureThe solution was cooled
  6. additiondiluted with dichloromethane-methanol
  7. washThe resin was washed with methanol
  8. concentrationThe basic fractions were concentrated
  9. customthe residue was purified by preparative TLC
  10. washeluting with 10% methanol-dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-0804fe412dab400ca4fef4483da56b84
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08058045B2

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