Ammonia → HCID 68277908, compound

HRID 522627Notes

Reaction equation

HRID 522627 reaction equation
[OH:1][C:2]([C:8]1[S:9][CH:10]=[C:11]([CH3:13])[N:12]=1)([CH3:7])[C:3]([NH:5][NH2:6])=O.[F:14][C:15]1[C:16]([CH2:22][N:23]2[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[S:30])=[N:24]2)=[N:17][CH:18]=[CH:19][C:20]=1[CH3:21].S(=O)(=O)(O)O.N>C(O)C.O.C(OCC)(=O)C>[F:14][C:15]1[C:16]([CH2:22][N:23]2[CH:27]=[CH:26][C:25]([NH:28][C:29]3[S:30][C:3]([C:2]([C:8]4[S:9][CH:10]=[C:11]([CH3:13])[N:12]=4)([OH:1])[CH3:7])=[N:5][N:6]=3)=[N:24]2)=[N:17][CH:18]=[CH:19][C:20]=1[CH3:21]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 1118Sulfuric AcidHCID 66752196HCID 66752196, compound2×HCID 86691619HCID 86691619, compound

Product 1

HCID 68277908HCID 68277908, compoundYield 68.3%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of Intermediate 107, 2-hydroxy-2-(4-methyl-1,3-thiazol-2-yl)propanohydrazide (82 mg, 0.407 mmol), and Intermediate 79, 3-fluoro-2-[(3-isothiocyanato-1H-pyrazol-1-yl)methyl]-4-methylpyridine (84 mg, 0.340 mmol) in ethanol (6 mL) was heated under reflux for 3 h. Reaction mixture was concentrated and residue was treated with sulfuric acid (2 mL, 37.5 mmol) at 0° C., and the resulting mixture was allowed to reach room temperature overnight. Reaction mixture was placed in an ice-bath and treated slowly and dropwise with 37% aq. NH3 (10 mL) until pH was basic. Mixture was diluted with water and ethyl acetate (60 mL). Organic phase was separated, washed with brine, dried over sodium sulfate and concentrated. Crude was loaded on a silica cartridge and eluted with a linear gradient, 0-5% MeOH-DCM, affording 100 mg (68.3% yield) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm: 10.81 (s, 1H), 8.19 (d, 1H), 7.71 (s, 1H), 7.33-7.31 (m, 1H), 7.27 (s, 1H), 7.19 (s, 1H), 5.93 (s, 1H), 5.33 (s, 2H), 2.28 (br s, 6H), 1.96 (s, 3H). [ES+MS] m/z 432 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 3 h
  3. customReaction mixture
  4. concentrationwas concentrated
  5. customReaction mixture
  6. customwas placed in an ice-bath
  7. customOrganic phase was separated
  8. washwashed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. washeluted with a linear gradient, 0-5% MeOH-DCM

Sources & evidence

ORD record
ord-12eac90dbdd4431990e830570b0e9312
Source dataset
uspto-grants-2016_05
Patent number
US09334265B2

Reaction notes

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