Hydrazine → (3s,6r)-1-[2-Amino-6-(3-Amino-2h-Indazol-6-Yl)pyrimidin-4-Yl]-6-Methyl-N-Phenylpiperidine-3-Carboxamide

HRID 2367418Notes

Reaction equation

HRID 2367418 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:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26](F)[CH:25]=2)[N:3]=1.[NH2:33][NH2:34]>CCO>[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:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:25]=[C:26]3[C:27]([C:30]([NH2:31])=[N:33][NH:34]3)=[CH:28][CH:29]=2)[N:3]=1

Participants

4

Reactant 2

HCID 9321HydrazineHCID 58504588(3S,6R)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-phenyl-3-piperidinecarboxamide

Product 1

HCID 50909915(3s,6r)-1-[2-Amino-6-(3-Amino-2h-Indazol-6-Yl)pyrimidin-4-Yl]-6-Methyl-N-Phenylpiperidine-3-CarboxamideYield 29.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-N-phenyl-3-piperidinecarboxamide (10 g, 23.2 mmol) in EtOH (400 mL) was added hydrazine (22.8 mL, 465 mmol). The resulting mixture was heated in seal tube at 100° C. overnight, cooled down, and concentrated in vacuo. The crude solution was purified by the silica gel chromatography (200 g column) eluting from 100% CHCl3 to CHCl3/CH3OH/NH4OH (9:1:0.1). The pure fractions that contained the desired product were combined and concentrated in vacuo to afford the title compound (3 g). LC-MS (ES) m/z=443 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.18 (d, J=6.8 Hz, 3H), 1.75 (s, 2H), 1.83 (m, 1H), 1.92 (m, 1H), 5.37 (s, 2H), 6.10 (s, 2H), 6.64 (s, 1H), 7.03 (s, 1H), 7.32 (s, 2H), 7.29-7.34 (m, 2H), 7.64 (d, J=7.3 Hz, 4H), 7.96 (s, 1H), 8.32 (s, 1H), 10.06 (s, 1H), 11.49 (s, 1H). The rest of fractions that contained the desired product and a small amount of impurities were combined, concentrated in vacuo and crystallized from CH3OH (˜10 mL). The crystalline material was obtained (3.6 g).

Workup

  1. temperaturecooled down
  2. concentrationconcentrated in vacuo
  3. customThe crude solution was purified by the silica gel chromatography (200 g column)
  4. washeluting from 100% CHCl3 to CHCl3/CH3OH/NH4OH (9:1:0.1)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f3c89f8f960647a3ae5929fa5f5d9117
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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