Ethanol → (3S,6R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-N-{[4-(methyloxy)phenyl]methyl}-3-piperidinecarboxamide

HRID 2367486Notes

Reaction equation

HRID 2367486 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]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:27]2[CH:32]=[CH:31][C:30]([C:33]#[N:34])=[C:29](F)[CH:28]=2)[N:3]=1.CCO.CCN(C(C)C)C(C)C.[NH2:48][NH2:49]>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]([O:25][CH3:26])=[CH:21][CH:20]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:27]2[CH:28]=[C:29]3[C:30]([C:33]([NH2:34])=[N:48][NH:49]3)=[CH:31][CH:32]=2)[N:3]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504502(3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-{[4-(methyloxy)phenyl]methyl}-3-piperidinecarboxamide

Product 1

HCID 58504803(3S,6R)-1-[2-amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-6-methyl-N-{[4-(methyloxy)phenyl]methyl}-3-piperidinecarboxamideYield 48.3%

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-(methyloxy)phenyl]methyl}-3-piperidinecarboxamide (203 mg, 0.43 mmol), 5 mL of EtOH, Hunig's base (0.30 mL, 1.71 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. 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 and washed by water, dried in vacuum, and then treated with EtOAc and CH3OH. The solid in the solvent was filtered, washed by EtOAc, and dried in vacuum to afford the title compound (101 mg) as a light yellow solid. LC-MS (ES) m/z=487 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.07-1.22 (m, 3H), 1.56-1.94 (m, 4H), 2.33 (m, 1H), 2.94 (m, 1H), 3.74 (s, 3H), 4.10-4.22 (m, 1H), 4.23-4.37 (m, 1H), 5.38 (s, 2H), 6.08 (s, 2H), 6.58 (s, 1H), 6.83-6.97 (m, 2H), 7.20 (d, J=8.6 Hz, 2H), 7.57 (dd, J=8.6, 1.26 Hz, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.98 (s, 1H) 8.36-8.48 (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. additiontreated with EtOAc and CH3OH
  6. filtrationThe solid in the solvent was filtered
  7. washwashed by EtOAc
  8. customdried in vacuum

Sources & evidence

ORD record
ord-d144d9b77dea4baf87713236d7c077c6
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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