Aluminium lithium hydride → (3-methyl-1-((1-methyl-1H-pyrazol-4-yl)methyl)-4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-5-yl)methanol

HRID 58115Notes

Reaction equation

HRID 58115 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[C:12]3[C:8]=2[CH:9]=[N:10][N:11]3C2CCCCO2)=[C:5]([C:26](OCC)=[O:27])[N:4]([CH2:31][C:32]2[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=2)[N:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1.CCOCC>[CH3:1][C:2]1[C:6]([C:7]2[CH:15]=[C:14]([C:16]([F:17])([F:19])[F:18])[CH:13]=[C:12]3[C:8]=2[CH:9]=[N:10][NH:11]3)=[C:5]([CH2:26][OH:27])[N:4]([CH2:31][C:32]2[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=2)[N:3]=1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 89782954HCID 89782954, compound

Product 1

HCID 71736513(3-methyl-1-((1-methyl-1H-pyrazol-4-yl)methyl)-4-(6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazol-5-yl)methanolYield 31.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A 100 mL round bottom flask was charged with ethyl 3-methyl-1-((1-methyl-1H-pyrazol-4-yl)methyl)-4-(1-(tetrahydro-2H-pyran-2-yl)-6-(trifluoromethyl)-1H-indazol-4-yl)-1H-pyrazole-5-carboxylate (0.745 g, 1.442 mmol) in THF (10 mL). The mixture was cooled to 0° C. A 1M solution of lithium aluminum hydride (4.33 mL, 4.33 mmol) in ether was added, and the reaction mixture was stirred at 0° C. for 1 hour. The reaction was quenched with 1N HCl (6 mL) at 0° C. and the product was extracted into EtOAc. The organic phase was washed with brine and dried over Na2SO4. The volatiles were removed by evaporation. The crude residue was dissolved in MeOH (5 mL). HCl (0.5 mL) was added and the mixture was stirred for 2 hours. The product was purified by LCMS, eluting with 30% ACN in H2O (containing 10 mM NH4HCO3) over a period of 10 minutes. The product-containing fractions were combined and the volatiles were evaporated using a GeneVac™ to give the title compound (0.178 g, 31.6%). 1H NMR (400 MHz, CD3OD) δ ppm 2.27 (s, 3H), 3.88 (s, 3H), 4.51 (s, 2H), 5.30 (s, 2H), 7.37 (d, J=1.26 Hz, 1H), 7.52 (s, 1H), 7.65 (s, 1H), 7.88 (s, 1H), 7.94-8.02 (m, 1H); ESI-MS m/z [M+H]+ calc'd for C18H17F3N6O, 391.15. found 391.13.

Workup

  1. customThe reaction was quenched with 1N HCl (6 mL) at 0° C.
  2. extractionthe product was extracted into EtOAc
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. customThe volatiles were removed by evaporation
  6. dissolutionThe crude residue was dissolved in MeOH (5 mL)
  7. additionHCl (0.5 mL) was added
  8. stirringthe mixture was stirred for 2 hours
  9. customThe product was purified by LCMS
  10. washeluting with 30% ACN in H2O (containing 10 mM NH4HCO3) over a period of 10 minutes
  11. customthe volatiles were evaporated

Sources & evidence

ORD record
ord-91b332cdd92e4712a18d8302117e8cd3
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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