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

HRID 2367490Notes

Reaction equation

HRID 2367490 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]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]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]>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][C@@H:18]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]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

7

Reactant 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504811(3S,6R)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-[(1R)-1-cyclohexylethyl]-6-methyl-3-piperidinecarboxamide

Product 1

HCID 58504746(3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-[(1R)-1-cyclohexylethyl]-6-methyl-3-piperidinecarboxamideYield 50.8%

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]-N-[(1R)-1-cyclohexylethyl]-6-methyl-3-piperidinecarboxamide (195.6 mg, 0.421 mmol), 5 mL of EtOH, Hunig's base (0.294 mL, 1.684 mmol), and hydrazine anhydrous (0.079 mL, 2.53 mmol) were added, and the yellow suspension mixture was heated overnight at 110° C. in an oil bath. 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 is heavier than 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 to afford the title compound (102 mg) as a light yellow solid. LC-MS (ES) m/z=477 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 0.83-1.36 (m, 12H), 1.55-1.85 (m, 9H), 2.20-2.37 (m, 1H), 2.92 (m, 1H), 3.56-3.71 (m, 1H), 5.38 (s, 2H), 6.07 (s, 2H), 6.57 (s, 1H), 7.54-7.61 (m, 1H), 7.66-7.78 (m, 2H), 7.94 (s, 1H), 11.50 (s, 1H).

Workup

  1. customa solid formed
  2. filtrationThe solid was filtered
  3. washwashed by water
  4. customdried in vacuum
  5. customThe solid was recrystallized
  6. filtrationthe solid in the solvent was filtered
  7. washwashed by EtOAc and CH3CN
  8. customdried in vacuum

Sources & evidence

ORD record
ord-6a5d0ff2ef874331a3195f9ee4d6d403
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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