Pyridine → tert-butyl 3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenylcarbamate

HRID 1887042Notes

Reaction equation

HRID 1887042 reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:25])[N:6]2[C:11]1[CH:12]=[C:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:14]=[CH:15][CH:16]=1.[O:26]([C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.N1C=CC=CC=1>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Cu+2]>[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]([C:36]1[CH:37]=[CH:38][C:33]([O:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:34][CH:35]=1)[C:5](=[O:25])[N:6]2[C:11]1[CH:12]=[C:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 27343774-Phenoxyphenylboronic acidHCID 86691212tert-butyl 3-(6-amino-8-oxo-7H-purin-9(8H)-yl)phenylcarbamate

Product 1

HCID 86761988tert-butyl 3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenylcarbamateYield 45%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
37 °C

Procedure

To a stirred mixture of tert-butyl 3-(6-amino-8-oxo-7H-purin-9(8H)-yl)phenylcarbamate (5) (600 mg, 1.8 mmol) and 400 mg 4 Å MS in 16 mL dry DMF were added 4-phenoxyphenylboronic acid (1.05 g, 4.9 mmol), Cu(OAc)2 (320 mg, 1.8 mmol) and pyridine (1 mL, 12.7 mmol). The reaction mixture was heated at 37° C. for 5 hrs under an O2 atmosphere. After cooling down to rt, the reaction mixture was filtered through a Celite pad. The filtrate was diluted with water (100 mL) and extracted with EtOAc (50 mL×3). The combined organic layer was washed with water (100 mL×2) and brine (100 mL×1), dried over Na2SO4, then concentrated to dryness. The residue was purified by column chromatography (silica gel, 0 to 5% methanol in DCM) to give tert-butyl 3-(6-amino-8-oxo-7-(4-phenoxyphenyl)-7H-purin-9(8H)-yl)phenylcarbamate (6) (404 mg, 45%) as a brown solid. LC-MS (ESI): m/z (M+1) 511.

Workup

  1. temperatureAfter cooling down to rt
  2. filtrationthe reaction mixture was filtered through a Celite pad
  3. additionThe filtrate was diluted with water (100 mL)
  4. extractionextracted with EtOAc (50 mL×3)
  5. washThe combined organic layer was washed with water (100 mL×2) and brine (100 mL×1)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by column chromatography (silica gel, 0 to 5% methanol in DCM)

Sources & evidence

ORD record
ord-d1f000d0298743d093428c9559504789
Source dataset
uspto-grants-2013_08
Patent number
US08501724B1

Reaction notes

Loading…