Cesium carbonate → HCID 67406947, compound

HRID 869296Notes

Reaction equation

HRID 869296 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]([CH3:14])[C:12](=[O:15])[C:11]([O:16]CC3C=CC(OC)=CC=3)=[CH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.I[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>CN1C(=O)CCC1.O.[Cu]I>[OH:16][C:11]1[C:12](=[O:15])[N:13]([CH3:14])[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([O:1][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[CH:3]=2)=[N:9][CH:10]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 696764-IodoanisoleHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 67406094HCID 67406094, compound

Product 1

HCID 67406947HCID 67406947, compoundYield 26.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

To a solution of 40.0 mg (0.118 mmol) 2-(3-hydroxyphenyl)-5-[(4-methoxybenzyl)oxy]-3-methylpyrimidin-4(3H)-one in 1 ml NMP was added 27.6 mg (0.118 mmol) 4-iodoanisole, 46.2 mg (0.142 mmol) Cs2CO3, 2.18 μl (0.012 mmol) 2,2,6,6-tetramethyl-3,5-heptanedione, and 5.85 mg (0.059 mmol) copper(I) iodide. The reaction mixture was heated to 180° C. for 30 min in microwave, diluted with 2 ml water, extracted with 10 ml EtOAc, and concentrated in vacuo. The oil was dissolved in 1 ml CH2Cl2, 1 ml TFA was added, and then concentrated in vacuo. Purification by mass-guided high throughput purification gave 10.0 mg (26% yield) of 5-hydroxy-2-[3-(4-methoxyphenoxy)phenyl]-3-methylpyrimidin-4(3H)-one. 1H NMR δ (ppm) (DMSO-d6): 7.50 (1H, s), 7.45 (1H, t, J=7.93 Hz), 7.25 (1H, d, J=7.66 Hz), 7.09-7.02 (4H, m), 6.98 (2H, d, J=8.74 Hz), 3.75 (3H, s), 2.54 (3H, s). HRMS (ESI positive) calc M+H=325.1181 found 325.11.

Workup

  1. extractionextracted with 10 ml EtOAc
  2. concentrationconcentrated in vacuo
  3. dissolutionThe oil was dissolved in 1 ml CH2Cl2
  4. addition1 ml TFA was added
  5. concentrationconcentrated in vacuo
  6. customPurification by
  7. custommass-guided high throughput purification

Sources & evidence

ORD record
ord-51f8d412c229459cb2db29dba7188f79
Source dataset
uspto-grants-2015_03
Patent number
US08969364B2

Reaction notes

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