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

HRID 2367498Notes

Reaction equation

HRID 2367498 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][C:22]([F:25])=[CH:21][CH:20]=3)=[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][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)=[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 58504621HCID 58504621, compound

Product 1

HCID 58504399(3S,6R)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-[(4-fluorophenyl)methyl]-6-methyl-3-piperidinecarboxamideYield 42.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

In a microwave tube, (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-[(4-fluorophenyl)methyl]-6-methyl-3-piperidinecarboxamide (192.5 mg, 0.416 mmol), 5 mL of EtOH, Hunig's base (0.291 ml, 1.665 mmol), and hydrazine anhydrous (0.078 mL, 2.497 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 light yellow title compound (84 mg). LC-MS (ES) m/z=475 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.08-1.24 (m, 3H), 1.58-2.01 (m, 4H), 2.22-2.42 (m, 1H), 2.94 (m, 1H), 4.16-4.42 (m, 2H), 5.38 (s, 2H), 6.08 (s, 2H), 6.55-6.65 (m, 1H), 7.12-7.24 (m, 2H), 7.27-7.39 (m, 2H), 7.58 (dd, J=8.5, 1.1 Hz, 1H), 7.70 (d, J=8.6 Hz, 1H), 7.95 (s, 1H), 8.50 (m, 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-0cd51f08c5b74c22b939f83784e65fdd
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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