Sulfuric acid magnesium salt (1:1) → Tak-071

HRID 629437Notes

Reaction equation

HRID 629437 reaction equation
[N:1]1([C:6]2[CH:26]=[CH:25][C:9]([CH2:10][C:11]3[C:12]([CH3:24])=[C:13]([F:23])[C:14]([CH:21]=O)=[C:15]([CH:20]=3)[C:16](OC)=[O:17])=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.[NH2:27][C@@H:28]1[C@@H:33]([OH:34])[CH2:32][CH2:31][O:30][CH2:29]1.S([O-])([O-])(=O)=O.[Mg+2]>C1COCC1>[F:23][C:13]1[C:12]([CH3:24])=[C:11]([CH2:10][C:9]2[CH:8]=[CH:7][C:6]([N:1]3[CH:5]=[CH:4][CH:3]=[N:2]3)=[CH:26][CH:25]=2)[CH:20]=[C:15]2[C:14]=1[CH2:21][N:27]([C@@H:28]1[C@@H:33]([OH:34])[CH2:32][CH2:31][O:30][CH2:29]1)[C:16]2=[O:17]

Participants

5

Reactant 3

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 55285677(3S,4S)-3-Aminotetrahydro-2H-pyran-4-OLHCID 118468398methyl 5-(4-(1H-pyrazol-1-yl)benzyl)-3-fluoro-2-formyl-4-methylbenzoate

Product 1

HCID 92042879Tak-071Yield 43.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 5-(4-(1H-pyrazol-1-yl)benzyl)-3-fluoro-2-formyl-4-methylbenzoate (0.21 g), (3S,4S)-3-aminotetrahydro-2H-pyran-4-ol (0.07 g), anhydrous magnesium sulfate (0.14 g) and THF (4.00 mL) was stirred at room temperature for 6 hr under nitrogen atmosphere. The insoluble substance was removed by filtration, and the filtrate was concentrated. The residue was dissolved in a mixed solvent of methanol (4.00 mL)-THF (4.00 mL), sodium triacetoxyborohydride (0.25 g) was added thereto, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (0.11 g).

Workup

  1. customThe insoluble substance was removed by filtration
  2. concentrationthe filtrate was concentrated
  3. dissolutionThe residue was dissolved in a mixed solvent of methanol (4.00 mL)-THF (4.00 mL), sodium triacetoxyborohydride (0.25 g)
  4. additionwas added
  5. stirringthe mixture was stirred at room temperature for 16 hr
  6. additionThe reaction mixture was diluted with ethyl acetate
  7. washthe mixture was washed with water and saturated brine
  8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-67696c22b248434f93058c815b8618ac
Source dataset
uspto-grants-2016_04
Patent number
US09315458B2

Reaction notes

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