Ethanol → HCID 66990798, compound

HRID 2367580Notes

Reaction equation

HRID 2367580 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][C@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])=[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][C@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])=[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 66990793HCID 66990793, compound

Product 1

HCID 66990798HCID 66990798, compoundYield 62.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
110 °C

Procedure

Into a sealable tube, (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-[(1S)-1-phenylethyl]-3-piperidinecarboxamide (186 mg, 0.406 mmol), EtOH (5 mL), Hunig's base (0.071 ml, 0.406 mmol), and hydrazine anhydrous (0.076 mL, 2.434 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 (120 mg) as a light yellow solid. LC-MS (ES) m/z=471 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.14 (d, J=6.8 Hz, 3H), 1.36 (d, J=7.1 Hz, 3H), 1.66 (m, 1H), 1.68 (m, 1H), 1.77 (m, 2H), 2.34 (m, 1H), 4.94 (m, 1H), 5.38 (s, 2H), 6.07 (s, 2H), 6.56 (s, 1H), 7.19-7.30 (m, 1H), 7.36 (m, 4H), 7.56 (dd, J=8.6, 1.5 Hz, 1H), 7.70 (d, J=8.34 Hz, 1H), 7.94 (s, 1H), 8.39 (d, J=8.1 Hz, 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-5d73e41d63354f71b9634af5c6d243fd
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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