Ethanol → HCID 58504422, compound

HRID 2367466Notes

Reaction equation

HRID 2367466 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]([O:23][CH3:24])[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.CCO.CCN(C(C)C)C(C)C.[NH2:46][NH2:47]>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]([O:23][CH3:24])[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:46][NH:47]3)=[CH:29][CH:30]=2)[N:3]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 9321HydrazineHCID 81531DiisopropylethylamineHCID 58504517HCID 58504517, compound

Product 1

HCID 58504422HCID 58504422, compoundYield 46.1%

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-(methyloxy)phenyl]-3-piperidinecarboxamide (190 mg, 0.426 mmol), 3 mL of EtOH, Hunig's base (0.223 l, 1.277 mmol), and hydrazine anhydrous (0.053 ml, 1.702 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 (90 mg) as a light yellow solid. LC-MS (ES) m/z=459 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.45 (m, 1H), 1.61-1.85 (m, 2H), 2.01 (m, 1H), 2.79-3.06 (m, 2H), 3.74 (s, 3H), 4.36-4.79 (m, 2H), 5.37 (s, 2H), 6.02-6.15 (s, 2H), 6.55-6.74 (m, 2H), 7.09-7.26 (m, 2H), 7.32-7.41 (m, 1H), 7.51-7.78 (m, 2H), 7.91-8.00 (m, 1H), 10.01 (s, 1H), 11.50 (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-47580603f55c43eebf5ab277e11ccbdf
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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