Ethanol → (3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-N-(2-methylcyclohexyl)-3-piperidinecarboxamide

HRID 2367594Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2367594
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]3[CH3:24])=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27](F)[CH:26]=2)[N:3]=1.CCO.CCN(C(C)C)C(C)C.[NH2:46][NH2:47]>CO>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([C:15]([NH:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]3[CH3:24])=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:25]2[CH:26]=[C:27]3[C:28]([C:31]([NH2:32])=[N:46][NH:47]3)=[CH:29][CH:30]=2)[N:3]=1

Komponenten

6

Edukt 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504821HCID 58504821, Verbindung

Produkt 1

HCID 58504758(3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-N-(2-methylcyclohexyl)-3-piperidinecarboxamideAusbeute 61,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

Into a microwave tube, (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-(2-methylcyclohexyl)-3-piperidinecarboxamide (192 mg, 0.426 mmol), EtOH (5 mL), Hunig's base (0.074 ml, 0.426 mmol), and hydrazine anhydrous (0.08 mL, 2.56 mmol) were added, and the yellow suspension mixture was heated overnight at 110° C. in an oil bath. When the temperature of the reaction reached to 100° C., the solid in the mixture was all dissolved. After overnight, there was a yellow solution as well as a little amount of black colored solid formed. LCMS showed mainly product. CH3OH (5 mL) was added to the solution. The black solid was filtered from the yellow solution. Water (20 mL) was added to the yellow solution, and a solid was formed. The solid was filtered, washed by water, and dried in vacuum. The solid was recrystallized from CH3CN, and the solid was filtered, washed by CH3CN, and dried in vacuum to afford the title compound (122 mg) as a light yellow solid. LC-MS (ES) m/z=463 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.68-0.98 (m, 4H), 1.14 (m, 8H), 1.66 (m, 8H), 2.25 (m, 1H), 3.30 (m, 1H), 3.36 (m, 1H), 5.38 (s, 2H), 6.07 (s, 2H), 6.56 (d, J=3.5 Hz, 1H), 7.51-7.65 (m, 1H), 7.70 (s, 1H), 7.73 (s, H), 7.94 (d, J=2.8 Hz, 1H), 11.50 (s, 1H).

Aufarbeitung

  1. customreached to 100° C.
  2. customformed
  3. filtrationThe black solid was filtered from the yellow solution
  4. additionWater (20 mL) was added to the yellow solution
  5. customa solid was formed
  6. filtrationThe solid was filtered
  7. washwashed by water
  8. customdried in vacuum
  9. customThe solid was recrystallized from CH3CN
  10. filtrationthe solid was filtered
  11. washwashed by CH3CN
  12. customdried in vacuum

Quellen und Nachweise

ORD-Eintrag
ord-8017faf069f542288c2c62a88116aa27
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697685B2

Notizen zur Reaktion

Wird geladen…