Tetrahydrothiopyran-4-one → 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-ol

HRID 1040170Notes

Reaction equation

HRID 1040170 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:5]=[C:6]([C:8]2[S:12][CH:11]=[N:10][CH:9]=2)[CH:7]=1.C([N-]C(C)C)(C)C.[Li+].[S:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1>C1COCC1>[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[S:12][C:11]([C:35]3([OH:38])[CH2:36][CH2:37][S:32][CH2:33][CH2:34]3)=[N:10][CH:9]=2)[CH:5]=[C:4]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:21])([F:23])[F:22])[CH:17]=[CH:16][N:15]=2)[CH:3]=1

Participants

5

Reactant 3

HCID 66173Tetrahydrothiopyran-4-oneHCID 2724682Lithium diisopropylamideHCID 58456403N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine2×

Product 1

HCID 672569944-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-olYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (Intermediate 4, 1.50 g, 4.46 mmol) in THF (10 mL) was added dropwise to a solution of lithium diisopropylamide (7.43 ml, 13.38 mmol) in THF (15 mL) at −78° C. and the resulting mixture was stirred at −78° C. for 30 minutes. Tetrahydrothiopyran-4-one (0.57 g, 4.91 mmol) in THF (5 mL) was then added, the dry ice bath was removed and the reaction was allowed to warm to room temperature. The reaction was quenched with aqueous saturated NH4Cl solution, and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Flash chromatography (SiO2, gradient elution 0 to 30% EtOAc in toluene) afforded 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-ol (1.21 g, 2.67 mmol, 60% yield) as a yellow foam. MS ESI: [M+H]+ m/z 453.0.

Workup

  1. customthe dry ice bath was removed
  2. temperatureto warm to room temperature
  3. customThe reaction was quenched with aqueous saturated NH4Cl solution
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. washFlash chromatography (SiO2, gradient elution 0 to 30% EtOAc in toluene)

Sources & evidence

ORD record
ord-5b59b970648d48389a7949f3dda2bd72
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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