Hydrazine → HCID 58504405, compound

HRID 2367426Notes

Reaction equation

HRID 2367426 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:24])[CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[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.[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:24])[CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:9]2)[CH:5]=[C:4]([C:25]2[CH:26]=[C:27]3[C:28]([C:31]([NH2:32])=[N:34][NH:35]3)=[CH:29][CH:30]=2)[N:3]=1

Participants

4

Reactant 2

HCID 9321HydrazineHCID 58504728HCID 58504728, compound

Product 1

HCID 58504405HCID 58504405, compoundYield 40.8%

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}-2-phenylacetamide (105 mg, 0.236 mmol) in ethanol (2 mL) into a 5 mL sealable vial was added hydrazine (0.22 mL, 7.1 mmol), and the reaction was then capped and heated on a hot plate at 100° C. overnight. 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 (30 ml/min, 15% CH3CN/H2O, 0.1% TFA to 45% 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, concentrated, and transferred to a haystack vial. Water (1 mL) was added, and the resulting mixture was freeze dried to afford the title compound (44 mg) as a light yellow solid. LC-MS (ES) m/z=457 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.15 (d, J=6.8 Hz, 3H), 1.61-1.76 (m, 4H), 2.57-2.68 (m, 1H), 3.44 (s, 2H), 3.59 (dd, J=7.7, 3.4 Hz, 1H), 4.38-4.84 (m, 2H), 5.38 (s, 2H), 6.11 (bs, 2H), 6.56 (s, 1H), 7.21-7.36 (m, 5H), 7.54 (dd, J=8.6, 1.0 Hz, 1H), 7.71 (d, J=8.3 Hz, 1H), 7.92 (s, 1H), 8.16 (d, J=8.1 Hz, 1H), 11.51 (s, 1H).

Workup

  1. customthe reaction was then capped
  2. concentrationThe reaction was concentrated
  3. dissolutionredissolved 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
  13. additionWater (1 mL) was added
  14. customdried

Sources & evidence

ORD record
ord-b0b8f6ded3a54b6c9ddd8f27a2c20c79
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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