Ethanol → HCID 58504692, compound

HRID 2367586Notes

Reaction equation

HRID 2367586 reaction equation
[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][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:26]2[CH:31]=[CH:30][C:29]([C:32]#[N:33])=[C:28](F)[CH:27]=2)[N:3]=1.CCO.CCN(C(C)C)C(C)C.[NH2:47][NH2:48]>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][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[F:25])=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:26]2[CH:27]=[C:28]3[C:29]([C:32]([NH2:33])=[N:47][NH:48]3)=[CH:30][CH:31]=2)[N:3]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504835HCID 58504835, compound

Product 1

HCID 58504692HCID 58504692, compoundYield 41.2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

Into a sealable vial, (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-[(2-fluorophenyl)methyl]-6-methyl-3-piperidinecarboxamide (189 mg, 0.409 mmol), EtOH (5 mL), Hunig's base (0.071 ml, 0.409 mmol), and hydrazine anhydrous (0.077 mL, 2.452 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 (80 mg) as a light yellow solid. LC-MS (ES) m/z=475 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.15 (d, J=6.8 Hz, 3H), 1.66 (m, 2H), 1.76 (m, 1H), 1.84 (m, 1H), 2.35 (m, 1H), 2.85 (m, 1H), 4.22-4.47 (m, 3H), 5.38 (s, 2H), 6.08 (s, 2H), 6.59 (s, 1H), 7.14-7.25 (m, 2H), 7.28-7.41 (m, 2H), 7.57 (m, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.94 (s, 1H), 8.45-8.54 (m, 1H), 11.50 (s, 1H).

Workup

  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

Sources & evidence

ORD record
ord-00e505e676d641a4a58643309af1a938
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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