Hydrazine hydrate (1:1) → HCID 66990451, compound

HRID 2367431Notes

Reaction equation

HRID 2367431 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]3[C@H:22]([C:23]([F:26])([F:25])[F:24])[CH2:21][CH2:20][C@H:19]([C:27]([NH:29][CH:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)=O)[CH2:18]3)[CH:10]=2)=[CH:5][C:4]=1F)#[N:2].[OH2:36].[NH2:37][NH2:38]>C(O)C>[NH2:2][C:1]1[C:3]2[C:4](=[CH:5][C:6]([C:9]3[N:14]=[C:13]([NH:15][CH3:16])[N:12]=[C:11]([N:17]4[C@H:22]([C:23]([F:26])([F:25])[F:24])[CH2:21][CH2:20][C@H:19]([C:27]([NH:29][CH:30]5[CH2:31][CH2:32][CH2:33][CH2:34]5)=[O:36])[CH2:18]4)[CH:10]=3)=[CH:7][CH:8]=2)[NH:38][N:37]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 66991246HCID 66991246, compound

Product 1

HCID 66990451HCID 66990451, compoundYield 53.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To cis-1-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-cyclopentyl-6-(trifluoromethyl)-3-piperidinecarboxamide (37 mg, 0.075 mmol) in ethanol (2 mL) was added hydrazine monohydrate (0.11 mL, 2.26 mmol) into a 5 mL sealable vial, and the reaction was capped and heated overnight at 100° C. The reaction was concentrated, then redissolved in 1 mL of DMSO and purified on HPLC (HPLC condition: open-access Gilson using Unipoint software with a Varian Polaris 5u C18(2) 100A, 50×30.00 mm 5 micron. 10-minute run (35 ml/min, 25% CH3CN/H2O, 0.1% TFA to 50% CH3CN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were combined, and the volume was reduced by reduce pressure until most of the CH3CN was removed. To the resulting aqueous mixture was added saturated aqueous NaHCO3 (10 mL) solution. The mixture was then extracted with EtOAc (3×10 mL). The organics were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The resulting material was transferred to a vial and water was added to freeze dried overnight and afford the title compound (20 mg) as a light yellow solid. LC-MS (ES) m/z=503 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.30-1.45 (m, 3H), 1.47-1.58 (m, 2H), 1.64 (dd, J=8.3, 4.3 Hz, 2H), 1.73-1.87 (m, 5H), 2.08 (bs, 1H), 2.33 (d, J=1.8 Hz, 1H), 2.84 (bs, 3H), 3.94-4.07 (m, 1H), 5.39 (s, 2H), 6.78 (bs, 2H), 7.62-7.74 (m, 2H), 7.94 (d, J=7.1 Hz, 1H), 8.02 (bs, 1H), 11.52 (s, 1H).

Workup

  1. customthe reaction was capped
  2. concentrationThe reaction was concentrated
  3. dissolutionredissolved in 1 mL of DMSO
  4. custompurified on HPLC (HPLC condition
  5. custom10-minute
  6. customwas removed
  7. additionTo the resulting aqueous mixture was added saturated aqueous NaHCO3 (10 mL) solution
  8. extractionThe mixture was then extracted with EtOAc (3×10 mL)
  9. washwashed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. additionwas added
  14. customto freeze dried overnight

Sources & evidence

ORD record
ord-5467d6949e594e8f894028bb42804f41
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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