Hydrazine → (3S)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-(2-methylphenyl)-3-piperidinecarboxamide

HRID 2367460Notes

Reaction equation

HRID 2367460 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH3:23])=[O:15])[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.CCN(C(C)C)C(C)C.[NH2:42][NH2:43]>CCO>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([C:14]([NH:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[CH3:23])=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:25]=[C:26]3[C:27]([C:30]([NH2:31])=[N:42][NH:43]3)=[CH:28][CH:29]=2)[N:3]=1

Participants

5

Reactant 3

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504438(3S)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(2-methylphenyl)-3-piperidinecarboxamide

Product 1

HCID 58504459(3S)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-(2-methylphenyl)-3-piperidinecarboxamideYield 54.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
150 °C

Procedure

Into a microwave tube, (3S)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(2-methylphenyl)-3-piperidinecarboxamide (90 mg, 0.209 mmol), 3 mL of EtOH, Hunig's base (0.11 mL, 0.627 mmol), and hydrazine anhydrous (0.026 mL, 0.836 mmol) were added, and the yellow mixture was heated at 150° C. for 150 minutes under microwave conditions. The solution turned black. LCMS showed mainly product with 10% of remaining starting material. The black solids were filtered and the yellow filtrate was evaporated. The resulting yellow residue was dissolved in CH3OH, and purified by HPLC (CH3CN/H2O w/0.1% HCO2H) to afford a formic acid salt of the title compound (50 mg) as a light yellow solid. LC-MS (ES) m/z=443 [M+H]+. 1H NMR (400 MHz, CD3OD): δ 1.73 (m, 1H), 1.91-2.15 (m, 2H), 2.26 (m, 4H), 2.70-2.92 (m, 1H), 3.44 (m, 1H), 3.50-3.84 (m, 1H), 4.30 (d, J=12.6 Hz, 1H), 4.67-5.11 (m, 1H), 6.79-6.95 (m, 1H), 7.09-7.33 (m, 4H), 7.47 (d, J=7.8 Hz, 1H), 7.83 (s, 1H) 7.99 (m, 1H).

Workup

  1. filtrationThe black solids were filtered
  2. customthe yellow filtrate was evaporated
  3. dissolutionThe resulting yellow residue was dissolved in CH3OH
  4. custompurified by HPLC (CH3CN/H2O w/0.1% HCO2H)

Sources & evidence

ORD record
ord-7b5ad8f759314338b5157b341b2918c5
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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