Hydrazine hydrate (1:1) → HCID 58504693, compound

HRID 2367326Notes

Reaction equation

HRID 2367326 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][O:11][C@H:10]([CH2:15][NH:16][C:17](=[O:24])[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.O.[NH2:35][NH2:36].C([O-])(O)=O.[Na+]>C(O)C>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][O:11][C@H:10]([CH2:15][NH:16][C:17](=[O:24])[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:35][NH:36]3)=[CH:29][CH:30]=2)[N:3]=1

Participants

5

Reactant 3

HCID 24654Hydrazine hydrate (1:1)HCID 516892Sodium BicarbonateHCID 58504567HCID 58504567, compound

Product 1

HCID 58504693HCID 58504693, compoundYield 44.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of crude N-({(2R,5R)-4-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-5-methyl-2-morpholinyl}methyl)benzamide (0.23 mmol theoretical) and hydrazine monohydrate (0.25 mL, 5.14 mmol) in ethanol (3 mL) was stirred at 100° C. in a sealed tube for 15 hours. The mixture was cooled, poured into saturated aqueous NaHCO3 (15 mL), and extracted with EtOAc (2×10 mL). The extracts were washed with brine (10 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified on a Gilson reverse phase HPLC (CH3CN/water with 0.1% TFA). The product fractions were concentrated in vacuo, taken up in a small amount of CH3OH, and added to saturated aqueous NaHCO3 (25 mL). That mixture was extracted with 90/10 CH2Cl2/IPA (3×25 mL), and the extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford the title compound (47 mg) as a pale yellow solid. LC-MS (ES) m/z=459 [M+H]+. 1H NMR (400 MHz, DMSO-d6): δ 1.19 (d, J=6.8 Hz, 3H), 2.73-2.91 (m, 1H), 3.39-3.55 (m, 2H), 3.57-3.71 (m, 2H), 3.73-3.83 (m, 1H), 4.08-4.74 (bs, 2H), 5.39 (s, 2H), 6.14 (s, 2H), 6.57 (s, 1H), 7.45-7.51 (m, 2H), 7.51-7.60 (m, 2H), 7.72 (d, J=8.6 Hz, 1H), 7.90 (d, J=7.6 Hz, 2H), 7.95 (s, 1H), 8.68 (t, J=5.5 Hz, 1H), 11.53 (s, 1H).

Workup

  1. temperatureThe mixture was cooled
  2. extractionextracted with EtOAc (2×10 mL)
  3. washThe extracts were washed with brine (10 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified on a Gilson reverse phase HPLC (CH3CN/water with 0.1% TFA)
  8. concentrationThe product fractions were concentrated in vacuo
  9. additionadded to saturated aqueous NaHCO3 (25 mL)
  10. extractionThat mixture was extracted with 90/10 CH2Cl2/IPA (3×25 mL)
  11. dry with materialthe extracts were dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0f96b623e9304ee384f59eaaa537d851
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

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