Formic Acid → HCID 136387343, compound

HRID 718197Notes

Reaction equation

HRID 718197 reaction equation
C([O:8][CH2:9][C:10]([C:13]1[NH:17][C:16](=[O:18])[N:15]([C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]3[CH:31]=[CH:30][N:29]=[C:28]([C:32]4[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=4)[CH:27]=3)=[C:21]([CH3:38])[N:20]=2)[N:14]=1)([CH3:12])[CH3:11])C1C=CC=CC=1.C(O)=O>CCOC(C)=O.[Pd]>[OH:8][CH2:9][C:10]([C:13]1[NH:17][C:16](=[O:18])[N:15]([C:19]2[CH:24]=[CH:23][C:22]([O:25][C:26]3[CH:31]=[CH:30][N:29]=[C:28]([C:32]4[CH:33]=[N:34][N:35]([CH3:37])[CH:36]=4)[CH:27]=3)=[C:21]([CH3:38])[N:20]=2)[N:14]=1)([CH3:12])[CH3:11]

Participants

5

Reactant 2

HCID 284Formic AcidHCID 136641702HCID 136641702, compound

Product 1

HCID 136387343HCID 136387343, compoundYield 15.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

3-(1-(Benzyloxy)-2-methylpropan-2-yl)-1-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.41 g, 0.80 mmol), and palladium(0) on carbon (10% w/w, 0.20 g, 0.19 mmol) were combined in EtOAc (4.0 mL) under an atmosphere of Ar. The reaction flask was depressurized and back-filled with H2 (g). This process was repeated (2×) and the reaction mixture was stirred under a balloon of H2 (g) for 12 h. Formic acid (0.5 mL) was added and stirring was continued an additional 12 h at RT. The reaction mixture was transferred to a Parr hydrogenation shaker and reaction was continued under 40 psi H2 (g) atmosphere. After 5 h, the Pd was removed by filtration through a pad of diatomaceous earth and the filter cake was washed with EtOAc (4×25 mL). The combined filtrates were concentrated in vacuo. The residue was purified by silica gel chromatography (MeOH/DCM) to afford 3-(1-hydroxy-2-methylpropan-2-yl)-1-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-1H-1,2,4-triazol-5(4H)-one (0.053 g, 15%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.85-11.83 (m, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.26 (s, 1H), 7.96 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.69 (d, J=8.8 Hz, 1H), 7.18 (d, J=2.4 Hz, 1H), 6.65 (dd, J=5.7, 2.4 Hz, 1H), 4.92-4.91 (m, 1H), 3.84 (s, 3H), 3.45-3.43 (m, 2H), 2.33 (s, 3H), 1.20 (s, 6H); MS (ESI) m/z: 422.2 (M+H+).

Workup

  1. additionback-filled with H2 (g)
  2. stirringstirring
  3. waitwas continued an additional 12 h at RT
  4. customThe reaction mixture was transferred to a Parr hydrogenation shaker and reaction
  5. waitAfter 5 h
  6. customthe Pd was removed by filtration through a pad of diatomaceous earth
  7. washthe filter cake was washed with EtOAc (4×25 mL)
  8. concentrationThe combined filtrates were concentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-18be948df25b461b9ca24beff7774c42
Source dataset
uspto-grants-2015_11
Patent number
US09193719B2

Reaction notes

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