Hydrazine → HCID 58504526, compound

HRID 2367464Notes

Reaction equation

HRID 2367464 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]([O:23][CH3:24])=[CH:19][CH:18]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[C:27](F)[CH:26]=2)[N:3]=1.CCN(C(C)C)C(C)C.[NH2:43][NH2:44]>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][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:25]2[CH:26]=[C:27]3[C:28]([C:31]([NH2:32])=[N:43][NH:44]3)=[CH:29][CH:30]=2)[N:3]=1

Participants

5

Reactant 3

HCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504720HCID 58504720, compound

Product 1

HCID 58504526HCID 58504526, compoundYield 11.3%

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-(methyloxy)phenyl]-3-piperidinecarboxamide (190 mg, 0.426 mmol), 3 mL of EtOH, Hunig's base (0.223 mL, 1.28 mmol), and hydrazine anhydrous (0.053 ml, 1.702 mmol) were added, and the yellow mixture was heated to 150° C. for 180 minutes in microwave. The solution turned black. LCMS showed mainly product. The black solids were filtered and the yellow filtrate was evaporated. The resulting yellow residue was dissolved in CH3OH at 50° C., and EtOAc was used to triturate. When the solution turned slightly cloudy, it was cooled to room temperature to get pure crystallized light yellow title compound (22 mg). LC-MS (ES) m/z=459 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.46 (m, 1H), 1.65-1.84 (m, 2H), 1.98 (m, 1H), 2.79-3.06 (m, 2H), 3.72 (s, 3H), 4.49 (m, 1H), 4.68 (m, 1H), 5.37 (s, 2H), 6.10 (s, 2H), 6.68 (s, 1H), 6.88 (d, J=9.1 Hz, 2H), 7.53 (d, J=9.1 Hz, 2H), 7.58-7.65 (m, 1H), 7.66-7.78 (m, 1H), 7.97 (s, 1H), 9.87 (s, 1H), 11.49 (s, 1H).

Workup

  1. filtrationThe black solids were filtered
  2. customthe yellow filtrate was evaporated
  3. dissolutionThe resulting yellow residue was dissolved in CH3OH at 50° C.
  4. customto triturate
  5. temperaturewas cooled to room temperature

Sources & evidence

ORD record
ord-eb8268a143c5414ea4ab1b9f778c76df
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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