N,N-Dimethylglycine → Methyl {4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenoxy]phenyl}acetate

HRID 2237634Notes

Reaction equation

HRID 2237634 reaction equation
[NH2:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([C:13]3[CH:18]=[CH:17][C:16](I)=[CH:15][CH:14]=3)[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=1.C[CH:22]([C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1)[C:23]([OH:25])=[O:24].[C:33](=O)([O-])[O-].[Cs+].[Cs+].CN(C)CC(O)=O>O1CCOCC1.[Cu]I>[NH2:1][C:2]1[C:7]2[C:8](=[O:20])[N:9]([C:13]3[CH:18]=[CH:17][C:16]([O:32][C:29]4[CH:30]=[CH:31][C:26]([CH2:22][C:23]([O:25][CH3:33])=[O:24])=[CH:27][CH:28]=4)=[CH:15][CH:14]=3)[CH2:10][CH2:11][O:12][C:6]=2[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 673N,N-DimethylglycineHCID 10796Cesium carbonateHCID 1025262-(4-Hydroxyphenyl)propionic acidHCID 593025304-Amino-6-(4-iodophenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one

Product 1

HCID 59302515Methyl {4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenoxy]phenyl}acetate

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A stirred slurry of 4-amino-6-(4-iodophenyl)-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-5(6H)-one (38 mg, 0.10 mmol), methyl 4-hydroxyphenylacetic acid (25 mg, 0.15 mmol), cesium carbonate (78 mg, 0.24 mmol), N,N-dimethyl glycine (10.3 mg, 0.10 mmol) and copper (I) iodide (6 mg, 0.03 mmol) in p-dioxane (0.4 mL) were heated at 90° C. for 18 hours. The reaction mixture was cooled, concentrated in vacuo and chromatographed (0-5% methanol: chloroform) to afford the title compound as a solid, 2.4 mg. 1H NMR (400 MHz, CDCl3) δ 8.31 (s, 1H), 7.25 (d, 2H), 7.20 (d, 2H), 7.07 (d, 2H), 7.02 (d, 2H), 4.69 (m, 2H), 4.00 (m, 2H), 3.68 (s, 3H). m/z=421.2 (M+1). IC50 254 nM.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated in vacuo
  3. customchromatographed (0-5% methanol: chloroform)

Sources & evidence

ORD record
ord-6f4d127c55294f6abc927ddee51c1218
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

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