Hydrazine hydrate (1:1) → HCID 58504440, compound

HRID 2367424Notes

Reaction equation

HRID 2367424 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([NH:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[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.O.[NH2:34][NH2:35]>C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][CH2:11][C@H:10]([NH:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:25]=[C:26]3[C:27]([C:30]([NH2:31])=[N:34][NH:35]3)=[CH:28][CH:29]=2)[N:3]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58504584HCID 58504584, compound

Product 1

HCID 58504440HCID 58504440, compoundYield 19.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To N-{(3S,6R)-1-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-6-methyl-3-piperidinyl}benzamide (101 mg, 0.234 mmol) in ethanol (2 mL) into a 5 mL sealable vial was added hydrazine monohydrate (0.22 mL, 7.02 mmol), and the reaction was capped and heat overnight at 100° C. The reaction was concentrated, re dissolved 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 (30 ml/min, 15% CH3CN/H2O, 0.1% TFA to 40% CH3CN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were combined and the volume was reduced to remove most of the CH3CN. To the resulting aqueous mixture was added sat. aqueous NaHCO3, and then it was extracted with EtOAc (3×15 mL). The organic was washed with brine, dried over MgSO4, filtered and concentrated to afford the title compound (20 mg) as a light yellow solid. LC-MS (ES) m/z=443 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.19 (d, J=6.8 Hz, 3H), 1.24 (s, 1H), 1.66-1.93 (m, 5H), 2.54 (s, 1H), 3.89 (d, J=4.0 Hz, 1H), 5.39 (s, 2H), 6.13 (bs, 1H), 6.62 (s, 1H), 7.47-7.59 (m, 5H), 7.71 (d, J=8.6 Hz, 1H), 7.90 (d, J=7.1 Hz, 2H), 7.94 (s, 1H), 8.43 (d, J=8.1 Hz, 1H), 11.51 (bs, 1H).

Workup

  1. customthe reaction was capped
  2. concentrationThe reaction was concentrated
  3. dissolutionre dissolved in 1 mL of DMSO
  4. custompurified on HPLC (HPLC condition
  5. custom10-minute
  6. customto remove most of the CH3CN
  7. additionTo the resulting aqueous mixture was added sat. aqueous NaHCO3
  8. extractionit was extracted with EtOAc (3×15 mL)
  9. washThe organic was washed with brine
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-2250ed6623fe452ba4ceb92eae740d47
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…