Sodium Carbonate → HCID 178425199, compound

HRID 1500977Notes

Reaction equation

HRID 1500977 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[O:5][CH2:6][C:7]1[CH:25]=[CH:24][C:10]([C:11]([NH:13][CH2:14][C:15]2[C:16]([OH:23])=[N:17][C:18]([CH3:22])=[CH:19][C:20]=2[CH3:21])=[O:12])=[CH:9][CH:8]=1.CC1(C)C(C)(C)OB([C:37]2[CH:38]=[CH:39][C:40]([NH2:43])=[N:41][CH:42]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:43][C:40]1[N:41]=[CH:42][C:37]([C:2]2[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=2)[O:5][CH2:6][C:7]2[CH:25]=[CH:24][C:10]([C:11]([NH:13][CH2:14][C:15]3[C:16]([OH:23])=[N:17][C:18]([CH3:22])=[CH:19][C:20]=3[CH3:21])=[O:12])=[CH:9][CH:8]=2)=[CH:38][CH:39]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27565555-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amineHCID 178425194HCID 178425194, compound

Product 1

HCID 178425199HCID 178425199, compoundYield 37%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-((3-bromophenoxy)methyl)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide (80 mg, 0.18 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (40 mg, 0.43 mmol) and sodium carbonate (75 mg, 0.7 mmol), tetra(triphenylphosphine) palladium (23 mg, 0.02 mmol) in 1,4-dioxane (8 ml) and water (2 ml) was stirred for 15 hours at 90° C. under nitrogen atmosphere. After cooling to room temperature, the reaction mixture was concentrated to give a residue. The residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1) to give product 4-((3-(6-aminopyridin-3-yl)phenoxy)methyl)-N-((2-hydroxy-4,6-dimethylpyridin-3-yl)methyl)benzamide (30 mg, 37%) as a white solid. LRMS (M+H+) m/z: calcd 454.20. found 454. HPLC purity (214 nm): 97%. 1H NMR (300 MHz, d6-DMSO): δ 11.45 (s, 1H), 8.34 (t, J=4.5 Hz, 1H), 8.22 (s, 1H), 7.85-7.83 (m, 2H), 7.73-7.69 (m, 1H), 7.51-7.48 (m, 2H), 7.32-7.12 (m, 3H), 6.91-6.88 (m, 1H), 6.52 (d, J=8.7 Hz, 1H), 6.16 (s, 2H), 5.85 (s, 1H), 5.20 (s, 2H), 4.29 (d, J=4.5 Hz, 2H), 2.16 (s, 3H), 2.10 (s, 3H).

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated
  3. customto give a residue
  4. customThe residue was purified by column chromatography (silica gel, dichloromethane/methanol=20:1)

Sources & evidence

ORD record
ord-4bc7aa5eb1444911a55412f56d53a078
Source dataset
uspto-grants-2015_12
Patent number
US09206128B2

Reaction notes

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