Sodium Bicarbonate → HCID 117600635, compound

HRID 526563Notes

Reaction equation

HRID 526563 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].[CH3:25][O:26][C:27]1[C:32]([O:33][CH3:34])=[C:31](B(O)O)[CH:30]=[CH:29][N:28]=1.C(=O)(O)[O-].[Na+]>O1CCOCC1.O.CCOC(C)=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>[CH3:25][O:26][C:27]1[C:32]([O:33][CH3:34])=[C:31]([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])[CH:30]=[CH:29][N:28]=1

Participants

8

Reactant 3

HCID 516892Sodium BicarbonateHCID 49760401(2,3-Dimethoxypyridin-4-yl)boronic acidHCID 1176002516-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide

Product 1

HCID 117600635HCID 117600635, compoundYield 42.7%

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

Combined 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide (60.0 mg, 0.152 mmol), (2,3-dimethoxypyridin-4-yl)boronic acid (41.7 mg, 0.228 mmol), PdCl2(dppf)-CH2Cl2 Adduct (6.20 mg, 7.59 μmol), and sodium bicarbonate (63.8 mg, 0.759 mmol) in dioxane (1139 μl) and water (380 μl) and heated in a microwave reactor for 60 minutes at 110° C. The reaction mixture was diluted with 150 mL EtOAc and washed with 1 N HCl. Organic layers were collected, dried with sodium sulfate, and concentrated to a residue which was purified on a 60 g silica gel column and eluted with hexanes and EtOAc to give 6-(4-(2,3-dimethoxypyridin-4-yl)-5-methoxy-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide (29.4 mg, 42.7%) as a yellow oil. MS m/z [M+H]+ 454.4.

Workup

  1. washwashed with 1 N HCl
  2. customOrganic layers were collected
  3. dry with materialdried with sodium sulfate
  4. concentrationconcentrated to a residue which
  5. customwas purified on a 60 g silica gel column
  6. washeluted with hexanes and EtOAc

Sources & evidence

ORD record
ord-8040172a45eb4a789e1898cbd0424c67
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

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