Sodium Carbonate → 6-(4-(4-cyano-2-methylphenyl)-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide

HRID 579046

Reaction equation

HRID 579046 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([C:9]2[CH:24]=[CH:23][C:12]([C:13]([NH:15][CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[O:14])=[CH:11][N:10]=2)[C:6]=1[O:7][CH3:8].[C:25]([C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[C:29]([CH3:36])[CH:28]=1)#[N:26].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[C:25]([C:27]1[CH:32]=[CH:31][C:30]([C:2]2[CH:3]=[N:4][N:5]([C:9]3[CH:24]=[CH:23][C:12]([C:13]([NH:15][CH2:16][CH:17]4[CH2:22][CH2:21][O:20][CH2:19][CH2:18]4)=[O:14])=[CH:11][N:10]=3)[C:6]=2[O:7][CH3:8])=[C:29]([CH3:36])[CH:28]=1)#[N:26]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 16218401(4-Cyano-2-methyl-phenyl)boronic acidHCID 1176002516-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide

Product 1

HCID 1176010346-(4-(4-cyano-2-methylphenyl)-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamideYield 100.4%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Combined 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide (25 mg, 0.063 mmol), (4-cyano-2-methylphenyl)boronic acid (30.5 mg, 0.190 mmol), sodium carbonate (26.6 mg, 0.316 mmol), and PdCl2(dppf)-CH2Cl2 adduct (2.58 mg, 3.16 μmol) in dioxane (0.2 mL) and water (0.05 mL) and purged with nitrogen. The reaction mixture was heated in a microwave on high absorbance for 1 hour at 110° C., cooled to 23° C. and diluted with water (1 mL) to give a residue. The residue was extracted with EtOAc (2×1 mL), the organic layers were combined, washed with brine (0.5 mL), dried over Na2SO4, filtered through a Hydrophilic PTFE 0.45 um filter (Millipore Millex™-LCR), rinsed with EtOAc, and dried in vacuo to provide 6-(4-(4-cyano-2-methylphenyl)-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide (27.3 mg, 100% yield) as a brown oil. MS m/z [M+H]+ 432.5.

Workup

  1. temperaturecooled to 23° C.
  2. customto give a residue
  3. extractionThe residue was extracted with EtOAc (2×1 mL)
  4. washwashed with brine (0.5 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered through a Hydrophilic PTFE 0.45 um
  7. filtrationfilter (Millipore Millex™-LCR)
  8. washrinsed with EtOAc
  9. customdried in vacuo

Sources & evidence

ORD record
ord-409c2011b50f4d72bff8ea8e70a5f982
Source dataset
uspto-grants-2015_05
Patent number
US09040522B2

Linked notes

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