Ethanol → HCID 58504431, compound

HRID 2367504Notes

Reaction equation

HRID 2367504 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][CH:18]3[CH2:23][CH2:22][CH:21]([CH3:24])[CH2:20][CH2:19]3)=[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]>O.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][CH:21]([CH3:24])[CH2:20][CH2:19]3)=[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

Participants

7

Reactant 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504415HCID 58504415, compound

Product 1

HCID 58504431HCID 58504431, compoundYield 48.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

Into a microwave tube, (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-(4-methylcyclohexyl)-3-piperidinecarboxamide (192.2 mg, 0.427 mmol), 5 mL of EtOH, Hunig's base (0.298 mL, 1.706 mmol), and hydrazine anhydrous (0.080 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 100° C., the solid in the mixture was all dissolved. After overnight, there was a yellow suspension as well as some black colored solid formed. LCMS showed mainly product. CH3OH (5 mL) was added to the solution. The black solid and the yellow solution were carefully separated due to the black solid being heavier than the yellow solution. Water (20 mL) was added to the yellow solution, and a solid formed. The solid was filtered, washed by water, and dried in vacuum. The solid was recrystallized using CH3CN, and the solid in the solvent was filtered, washed by EtOAc and CH3CN, and dried in vacuum. The yellow residue was dissolved in CH3OH, and purified by HPLC to afford the light yellow title compound (95 mg). LC-MS (ES) m/z=509 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.81-1.04 (m, 4H), 1.08-1.37 (m, 6H), 1.40-1.86 (m, 10H), 2.16-2.44 (m, 1H), 2.92 (m, 1H), 3.78 (m, 1H), 5.38 (s, 2H), 6.08 (s, 2H), 6.56 (s, 1H), 7.57 (d, J=8.6 Hz, 1H), 7.67-7.82 (m, 2H), 7.88-7.99 (m, 1H), 8.16 (s, 1H).

Workup

  1. customreached 100° C.
  2. customformed
  3. customa solid formed
  4. filtrationThe solid was filtered
  5. washwashed by water
  6. customdried in vacuum
  7. customThe solid was recrystallized
  8. filtrationthe solid in the solvent was filtered
  9. washwashed by EtOAc and CH3CN
  10. customdried in vacuum
  11. dissolutionThe yellow residue was dissolved in CH3OH
  12. custompurified by HPLC

Sources & evidence

ORD record
ord-7f611c1fb4654a10ad813ba0bd617a37
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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