Hydrazine hydrate (1:1) → HCID 58504595, compound

HRID 2367626Notes

Reaction equation

HRID 2367626 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10](F)[CH:9]=2)[CH:5]=[C:4]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([N:23]3[CH2:27][CH2:26][O:25][C:24]3=O)[CH2:18]2)[N:3]=1.[OH2:29].[NH2:30][NH2:31]>C(O)C>[NH2:1][C:2]1[N:3]=[C:4]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([N:23]3[CH2:27][CH2:26][O:29][C:24]3=[O:25])[CH2:18]2)[CH:5]=[C:6]([C:8]2[CH:9]=[C:10]3[C:11]([C:12]([NH2:13])=[N:30][NH:31]3)=[CH:14][CH:15]=2)[N:7]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 58504634HCID 58504634, compound

Product 1

HCID 58504595HCID 58504595, compoundYield 43.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

Into a 5 mL sealable vial were added 4-{2-amino-6-[(3R)-3-(2-oxo-1,3-oxazolidin-3-yl)-1-piperidinyl]-4-pyrimidinyl}-2-fluorobenzonitrile (83 mg, 0.217 mmol) and ethanol (3 mL) followed by hydrazine monohydrate (0.319 mL, 6.51 mmol). The reaction vial was capped and was heated at 100° C. overnight. The reaction was concentrated, then dissolved in 2 mL of DMSO and purified on HPLC (HPLC condition: open-access Gilson using Trilution software with a Sunfire 5u C18(2) 100A. 50×30.00 mm 5 micron. 7.3-minute run (47 mL/min, 10% CH3CN/H2O, 0.1% TFA to 25% 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 water left behind was added saturated NaHCO3 and then extracted with EtOAc (5×100 mL). The organic was washed with brine, dried over MgSO4, filtered, concentrated, and transferred to a haystack vial. Water (1 mL) was added, and the resulting mixture was freeze dried to afford the title compound (37 mg) as a light yellow solid. LC-MS (ES) m/z=395 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.45-1.58 (m, 1H), 1.68-1.89 (m, 3H), 2.82 (t, J=11.6 Hz, 1H), 2.99 (t, J=11.8 Hz, 1H), 3.54 (ddd, J=11.1, 7.0, 4.2 Hz, 1H), 3.60 (dd, J=9.6, 8.6 Hz, 2H), 4.29 (td, J=8.0, 2.2 Hz, 2H), 4.40 (dd, 2H), 5.38 (s, 2H), 6.14 (bs, 2H), 6.63 (s, 1H), 7.57 (dd, J=8.3, 1.3 Hz, 1H), 7.71 (d, J=8.3 Hz, 1H), 7.95 (s, 1H), 11.52 (s, 1H).

Workup

  1. customThe reaction vial was capped
  2. concentrationThe reaction was concentrated
  3. dissolutiondissolved in 2 mL of DMSO
  4. custompurified on HPLC (HPLC condition
  5. custom7.3-minute
  6. customto remove most of the CH3CN
  7. waitTo the water left behind
  8. additionwas added saturated NaHCO3
  9. extractionextracted with EtOAc (5×100 mL)
  10. washThe organic was washed with brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. additionWater (1 mL) was added
  15. customdried

Sources & evidence

ORD record
ord-ea021a8da89549b3937eac19a90819b6
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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