Hydrazine → HCID 66991218, compound

HRID 2367645Notes

Reaction equation

HRID 2367645 reaction equation
[C:1]([C:3]1[C:8]([O:9][CH3:10])=[CH:7][C:6]([C:11]2[N:16]=[C:15]([NH:17][CH3:18])[N:14]=[C:13]([N:19]3[C@H:24]([CH3:25])[CH2:23][CH2:22][C@H:21]([C:26]([NH:28][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)=[O:27])[CH2:20]3)[CH:12]=2)=[CH:5][C:4]=1F)#[N:2].[NH2:37][NH2:38]>C(O)C>[NH2:2][C:1]1[C:3]2[C:4](=[CH:5][C:6]([C:11]3[N:16]=[C:15]([NH:17][CH3:18])[N:14]=[C:13]([N:19]4[C@H:24]([CH3:25])[CH2:23][CH2:22][C@H:21]([C:26]([NH:28][CH2:29][C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)=[O:27])[CH2:20]4)[CH:12]=3)=[CH:7][C:8]=2[O:9][CH3:10])[NH:38][N:37]=1

Participants

4

Reactant 2

HCID 9321HydrazineHCID 66991306HCID 66991306, compound

Product 1

HCID 66991218HCID 66991218, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

Dissolved (3S,6R)-1-[6-[4-cyano-3-fluoro-5-(methyloxy)phenyl]-2-(methylamino)-4-pyrimidinyl]-6-methyl-N-(phenylmethyl)-3-piperidinecarboxamide (96 mg, 0.196 mmol) with Ethanol (2 mL) in a 5 mL sealable vial then added hydrazine (0.185 mL, 5.89 mmol). The reaction was capped and heat overnight at 100° C. The reaction was concentrated then 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 (35 ml/min, 28% ACN/H2O, 0.1% TFA to 53% ACN/H2O, 0.1% TFA) with UV detection at 254 nm). Product fractions were pooled and the volume was reduced by reduce pressure until most of the MeCN was removed then the aqueous saturated NaHCO3 (10 mL) added. The mixture was then extracted with EtOAc (3×10 mL). The organic was pooled, washed with saturated. NaCl, dried over MgSO4, filtered, and concentrated. Then transferred in to 40 mL vial then water was added then freeze-dried to isolate 36 mg of off white solid. LC-MS (ES) m/z=501 [M+H]+. 1H NMR (400 MHz, DMSO-d6) d ppm 1.17 (d, J=7.07 Hz, 3H) 1.67 (d, J=3.54 Hz, 2H) 1.75 (dd, J=12.88, 3.03 Hz, 1H) 1.80-1.93 (m, 1H) 2.31-2.42 (m, 1H) 2.83 (d, J=4.55 Hz, 3H) 2.98 (br. s., 1H) 3.94 (s, 3H) 4.31 (dd, J=9.73, 5.94 Hz, 2H) 4.78 (br. s., 1H) 5.03 (br. s., 2H) 6.56 (br. s., 2H) 6.94 (br. s., 1H) 7.28 (d, J=7.07 Hz, 2H) 7.31-7.37 (m, 2H) 7.51 (br. s., 1H) 8.50 (t, J=5.94 Hz, 1H)

Workup

  1. customThe reaction was capped
  2. concentrationThe reaction was concentrated
  3. dissolutionthen dissolved in 1 mL of DMSO
  4. custompurified on HPLC (HPLC condition
  5. custom10-minute
  6. customwas removed
  7. additionthe aqueous saturated NaHCO3 (10 mL) added
  8. extractionThe mixture was then extracted with EtOAc (3×10 mL)
  9. washwashed with saturated
  10. dry with materialNaCl, dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. additionwater was added
  14. customthen freeze-dried
  15. customto isolate 36 mg of off white solid

Sources & evidence

ORD record
ord-0d92a76fa03842718ce7cf5d24d2cd2d
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…