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

HRID 2367448Notes

Reaction equation

HRID 2367448 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][C:20]([F:23])=[CH:19][CH:18]=3)=[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:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:29]=[C:28]3[C:27]([C:30]([NH2:31])=[N:42][NH:43]3)=[CH:26][CH:25]=2)[N:3]=1

Participants

5

Reactant 3

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504620(3S)-1-[2-Amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(4-fluorophenyl)-3-piperidinecarboxamide

Product 1

HCID 58504587(3S)-1-[2-Amino-6-(3-amino-1H-indazol-6-yl)-4-pyrimidinyl]-N-(4-fluorophenyl)-3-piperidinecarboxamideYield 21.6%

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-(4-fluorophenyl)-3-piperidinecarboxamide (90 mg, 0.207 mmol), 3 mL of EtOH, Hunig's base (0.11 mL, 0.621 mmol), and hydrazine anhydrous (0.026 mL, 0.829 mmol) were added, and the yellow mixture was heated at 150° C. for 150 minutes in microwave. 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 (20 mg) as a light yellow solid. LC-MS (ES) m/z=447 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.50 (m, 1H), 1.85 (m, 2H), 2.07 (m, 1H), 3.17 (m, 2H), 4.52 (m, 1H), 4.74 (m, 1H), 4.98 (m, 1H), 6.94-7.08 (m, 1H), 7.16 (m, 2H), 7.39 (s, 1H), 7.56-7.69 (m, 2H), 7.73 (s, 1H), 7.82-8.04 (m, 1H), 10.13 (m, 1H), 11.86-12.16 (m, 2H).

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-e384cf1201734a9ebc88ffa879b886e7
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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