Hydrazine hydrate (1:1) → HCID 46216155, compound

HRID 2367276Notes

Reaction equation

HRID 2367276 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]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[C:26](F)[CH:25]=2)[N:3]=1.O.[NH2:34][NH2:35]>C(O)C>[NH4+:1].[OH-:11].[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C@H:13]([CH3:14])[CH2:12][O:11][C@H:10]([C:15]([NH:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:16])[CH2:9]2)[CH:5]=[C:4]([C:24]2[CH:25]=[C:26]3[C:27]([C:30]([NH2:31])=[N:34][NH:35]3)=[CH:28][CH:29]=2)[N:3]=1

Participants

5

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 51353730HCID 51353730, compound

Product 2

HCID 14923Ammonium HydroxideHCID 46216155HCID 46216155, compoundYield 62.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

(2S,5R)-4-[2-amino-6-(4-cyano-3-fluorophenyl)-4-pyrimidinyl]-5-methyl-N-phenyl-2-morpholinecarboxamide (57 mg, 0.132 mmol) was dissolved in ethanol (3 mL) with stirring in a 5 mL microwave vessel. Hydrazine monohydrate (150 μL, 3.09 mmol) was added, and the mixture was capped and heated at 100° C. in an oil bath for 24 hours. The mixture was partitioned between EtOAc and water, and the aqueous layer was extracted with EtOAc. The combined organics were washed with brine, dried (MgSO4) filtered and evaporated. Purification by silica gel chromatograpy (Analogix RS-4 g) eluting with 90:10:1 CHCl3:CH3OH:conc. aq. NH4OH afforded the title compound (19 mg, 0.041 mmol, 30.8% yield) as a colorless film/foam. NMR showed a residual solvent peak with singlets at 1.9 and 3.36, so the material was azeotroped with CH3CN and then triturated to give a white powder. 1H NMR (400 MHz, DMSO-d6): δ 1.24 (d, J=6.3 Hz, 3H), 3.04 (bs, 1H), 3.82 (d, J=9.8 Hz, 1H), 3.93 (d, J=11.1 Hz, 1H), 4.07-4.23 (m, 1H), 4.53 (bs, 2H), 5.39 (bs, 2H), 6.22 (bs, 2H), 6.61 (s, 1H), 7.10 (t, J=7.1 Hz, 1H), 7.34 (t, J=7.7 Hz, 2H), 7.60 (d, J=8.3 Hz, 1H), 7.69-7.78 (m, 3H), 7.96 (s, 1H), 9.87 (bs, 1H), 11.52 (s, 1H).

Workup

  1. customthe mixture was capped
  2. customThe mixture was partitioned between EtOAc and water
  3. extractionthe aqueous layer was extracted with EtOAc
  4. washThe combined organics were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customPurification by silica gel chromatograpy (Analogix RS-4 g)
  9. washeluting with 90:10:1 CHCl3

Sources & evidence

ORD record
ord-08675f800d2d431d8abbfcb2d3dbcb7f
Source dataset
uspto-grants-2014_04
Patent number
US08697685B2

Reaction notes

Loading…