Magnesium 2-(dioxidan-2-ide-1-carbonyl)benzoate--water (1/1/6) → N-{3-[2-(4-fluoro-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

HRID 410674Notes

Reaction equation

HRID 410674 reaction equation
[F:1][C:2]1([C:8]2[S:9][C:10]([C:13]3[CH:14]=[C:15]([NH:20][C:21]4[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=4)[CH:16]=[C:17]([CH3:19])[CH:18]=3)=[CH:11][N:12]=2)[CH2:7][CH2:6][S:5][CH2:4][CH2:3]1.[OH2:31].[OH2:32].O.O.O.O.C(O[O-])(=O)C1C(=CC=CC=1)C([O-])=O.[Mg+2]>C(Cl)Cl.CO.[O-]S([O-])(=S)=O.[Na+].[Na+].O>[F:1][C:2]1([C:8]2[S:9][C:10]([C:13]3[CH:14]=[C:15]([NH:20][C:21]4[N:26]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:24]=[CH:23][N:22]=4)[CH:16]=[C:17]([CH3:19])[CH:18]=3)=[CH:11][N:12]=2)[CH2:3][CH2:4][S:5](=[O:32])(=[O:31])[CH2:6][CH2:7]1

Participants

6

Reactant 2

HCID 21894687Magnesium 2-(dioxidan-2-ide-1-carbonyl)benzoate--water (1/1/6)HCID 58456368N-{3-[2-(4-fluorotetrahydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 58456232N-{3-[2-(4-fluoro-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amineYield 79%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 24477Sodium ThiosulfateSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

N-{3-[2-(4-fluorotetrahydro-2H-thiopyran-4-yl)-1,3-thiazol-5-yl]-5-methylphenyl}-4-(trifluoromethyl)pyrimidin-2-amine (Example 132, 140 mg, 0.308 mmol) was dissolved in a 2:1 v/v CH2Cl2/MeOH mixture (6 mL) and magnesium monoperoxyphthalate hexahydrate (286 mg, 0.462 mmol) was added. The reaction was stirred at room temperature for 2 hrs, diluted with aqueous 10% Na2S2O3 and water and extracted with CH2Cl2 (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Column chromatography on silica (gradient elution, 0 to 50% EtOAc in hexanes) afforded the title compound (0.118 g, 0.243 mmol, 79% yield) as a white solid. MS ESI: [M+H]+ m/z 487.0. 1H NMR (500 MHz, DMSO-d6) δ 10.30 (s, 1H), 8.84 (d, J=4.9, 1H), 8.14 (d, J=2.7, 1H), 8.04 (bs, 1H), 7.48 (bs, 1H), 7.29 (d, J=4.9, 1H), 7.22 (bs, 1H), 3.48-3.40 (m, 2H), 3.28-3.24 (m, 2H), 2.75-2.60 (m, 4H), 2.32 (s, 3H). rhSYK activity=+++.

Workup

  1. additionwas added
  2. extractionextracted with CH2Cl2 (2×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-dbe04be6fd314dc38caef846f89a48b0
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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