Ethanol → HCID 58504671, compound

HRID 2367468Notes

Reaction equation

HRID 2367468 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]=[C:19]([Cl:23])[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.CCO.CCN(C(C)C)C(C)C.[NH2:45][NH2:46]>O.CCOC(C)=O>[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]=[C:19]([Cl:23])[CH:18]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:25]=[C:26]3[C:27]([C:30]([NH2:31])=[N:45][NH:46]3)=[CH:28][CH:29]=2)[N:3]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504417HCID 58504417, compound

Product 1

HCID 58504671HCID 58504671, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

Into a microwave tube, (3S)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-N-(3-chlorophenyl)-3-piperidinecarboxamide (190 mg, 0.421 mmol), 3 mL of EtOH, Hunig's base (0.22 mL, 1.26 mmol), and hydrazine anhydrous (0.053 mL, 1.69 mmol) were added, and the yellow mixture was heated at 150° C. for 180 minutes under microwave conditions. The solution turned black. LCMS showed mainly product. The black solids were filtered off and the yellow filtrate was evaporated. To the resulting brown liquid was added EtOAc (1 mL), and the mixture was warmed to 50° C. Two layers formed. The top layer is EtOAc solution, and it was pipeted to a different vial. The bottom layer is the comparatively pure product. This compound was treated with water at 50° C., and a solid was formed. This material was filtered and dried to give the title compound as a light yellow solid (150 mg). LC-MS (ES) m/z=463 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.45 (m, 1H), 1.63-1.85 (m, 2H), 2.01 (m, 1H), 2.79-3.06 (m, 2H), 4.62-4.76 (m, 1H), 5.37 (s, 2H), 6.11 (s, 2H), 6.69 (s, 1H), 7.10 (m, 1H), 7.28 (m, 1H), 7.52 (m, 1H), 7.55 (m, 1H), 7.79 (m, 1H), 7.82 (s, 1H), 8.03 (s, 1H), 10.22 (s, 1H), 11.45-11.57 (s, 1H).

Workup

  1. filtrationThe black solids were filtered off
  2. customthe yellow filtrate was evaporated
  3. additionTo the resulting brown liquid was added EtOAc (1 mL)
  4. temperaturethe mixture was warmed to 50° C
  5. customTwo layers formed
  6. customa solid was formed
  7. filtrationThis material was filtered
  8. customdried

Sources & evidence

ORD record
ord-1325357bfc7e48a3add8de20246a7e99
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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