Hydrazine hydrate (1:1) → HCID 66991086, compound

HRID 2367436Notes

Reaction equation

HRID 2367436 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[CH:22]([C:23]([F:26])([F:25])[F:24])[CH2:21][CH2:20][CH:19]([C:27]([NH:29][CH2:30][C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)=[O:28])[CH2:18]3)[CH:10]=2)=[CH:5][C:4]=1F)#[N:2].O.[NH2:39][NH2:40]>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:24])([F:26])[F:25])[CH2:21][CH2:20][C@H:19]([C:27]([NH:29][CH2:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)=[O:28])[CH2:18]4)[CH:10]=3)=[CH:7][CH:8]=2)[NH:40][N:39]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)2×HCID 58504579HCID 58504579, compound

Product 1

HCID 66991086HCID 66991086, compoundYield 39.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 1-[6-(4-cyano-3-fluorophenyl)-2-(methylamino)-4-pyrimidinyl]-N-(phenylmethyl)-6-(trifluoromethyl)-3-piperidinecarboxamide (66 mg, 0.129 mmol) in ethanol (2 mL) into a 5 mL microwave vial was added hydrazine monohydrate (0.121 mL, 3.86 mmol). The reaction was capped and heated overnight. Since the reaction was not completed, additional 50 uL of hydrazine monohydrate was added and heated overnight. The reaction was concentrated then 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 (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 under vacuum until most of the CH3CN was removed. Saturated aqueous NaHCO3 (10 mL) was added, and the resulting mixture was extracted with EtOAc (3×10 mL). The organics were combined, washed with brine, dried over MgSO4, filtered, and concentrated. The resulting material was transferred into a vial and water was added and freeze dried overnight to afford the title compound (27 mg) as a light yellow solid. LC-MS (ES) m/z=525 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.81-1.88 (m, 3H), 2.06-2.14 (m, 1H), 2.43-2.49 (m, 1H), 2.84 (bs, 3H), 3.14 (bs, 1H), 4.20-4.43 (m, 2H), 5.40 (s, 2H), 6.80 (bs, 1H), 7.22-7.31 (m, 3H), 7.31-7.38 (m, 2H), 7.62-7.69 (m, 1H), 7.71-7.75 (m, 1H), 8.02 (bs, 1H), 8.54 (t, J=5.9 Hz, 1H), 11.53 (s, 1H).

Workup

  1. customThe reaction was capped
  2. temperatureheated overnight
  3. temperatureheated overnight
  4. concentrationThe reaction was concentrated
  5. dissolutionthen re-dissolved in 1 mL of DMSO
  6. custompurified on HPLC (HPLC condition
  7. custom10-minute
  8. customwas removed
  9. additionSaturated aqueous NaHCO3 (10 mL) was added
  10. extractionthe resulting mixture was extracted with EtOAc (3×10 mL)
  11. washwashed with brine
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. additionwas added
  16. customfreeze dried overnight

Sources & evidence

ORD record
ord-f99dc4e579bd412b9299f0334c0e60be
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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