Phosphorus oxychloride → 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide

HRID 576800Notes

Reaction equation

HRID 576800 reaction equation
C([NH:8][C@H]1CCCC[C@H]1CO)C1C=CC=CC=1.[C:17]([C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29]([C:30]3[C:31](=[O:49])[N:32]([CH3:48])[C:33](=[O:47])[N:34]([C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=4)[C:35]=3[CH3:36])=[C:28]([S:50]([OH:53])(=O)=[O:51])[CH:27]=[N:26]2)=[CH:21][CH:20]=1)#[N:18].P(Cl)(Cl)(Cl)=O.O.N>C(#N)C.C(OCC)(=O)C.O.N1C=CC=CC=1>[C:17]([C:19]1[CH:24]=[CH:23][C:22]([N:25]2[C:29]([C:30]3[C:31](=[O:49])[N:32]([CH3:48])[C:33](=[O:47])[N:34]([C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([C:43]([F:46])([F:45])[F:44])[CH:38]=4)[C:35]=3[CH3:36])=[C:28]([S:50]([NH2:8])(=[O:53])=[O:51])[CH:27]=[N:26]2)=[CH:21][CH:20]=1)#[N:18]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 853687(+)-cis-2-BenzylaminocyclohexanemethanolHCID 12896473Azane;hydrateHCID 715138621-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonic acid

Product 1

HCID 712514151-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of (−)-cis-2-benzylaminocyclohexanemethanol salt of 1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonic acid (prepared in Example 195) (6.83 g) in acetonitrile (48 ml) were added pyridine (1.47 ml) and phosphorus oxychloride (3.39 ml) and the resulting mixture was stirred at room temperature for two hours. The reaction solution was added dropwise to ammonia water (28%, 48 ml) that cooled to 0° C. and the mixture was stirred for another ten minutes. To the reaction solution were added water (50 ml) and ethyl acetate (100 ml×2) such that the intended products were extracted into an organic layer. The organic layer was washed with 4% ammonia water (50 ml), saturated saline (20 ml), 1N hydrochloric acid (50 ml×2) and saturated saline (50 ml), dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford the same product as Example 209, (+)-1-(4-cyanophenyl)-5-(3,6-dimethyl-2,4-dioxo-1-(3-trifluoromethylphenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazole-4-sulfonamide (4.84 g). UPLC/MS 531 (M+H)/0.87 min. (measurement condition 9)

Workup

  1. temperaturecooled to 0° C.
  2. stirringthe mixture was stirred for another ten minutes
  3. extractionwere extracted into an organic layer
  4. washThe organic layer was washed with 4% ammonia water (50 ml), saturated saline (20 ml), 1N hydrochloric acid (50 ml×2) and saturated saline (50 ml)
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-1f596e44ac334c9cb5a4ce090608e140
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

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