Cesium carbonate → 2-(2,4-Dimethoxyphenyl)-6-(4-methoxybenzylamino)-9-isopropylpurine

HRID 348390Notes

Reaction equation

HRID 348390 reaction equation
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[N:3]=1.[CH3:24][O:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:27]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:24][O:25][C:26]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[CH:28][C:27]=1[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)[N:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27343412,4-Dimethoxybenzeneboronic acidHCID 98587852-Chloro-9-isopropyl-N-(4-methoxybenzyl)-9H-purin-6-amine

Product 1

HCID 111547492-(2,4-Dimethoxyphenyl)-6-(4-methoxybenzylamino)-9-isopropylpurineYield 96%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

Boronic Acid coupling reactions: A 10 mL flame-dried Schlenk flask equipped with a magnetic stir bar was charged with 2-chloro-6-(4-methoxybenzylamino)-9-isopropylpurine (0.193 g, 0.5 mmol, 1.0 equiv), 2,4-dimethoxyphenylboronic acid (0.136 g, 0.75 mmol, 1.5 equiv), Pd2(dba)3 (0.0069 g, 0.0075 mmol, 0.015 equiv.), ligand 1 (0.0051 g, 0.015 mmol, 0.03 equiv.) and Cs2CO3 (0.326 g, 1.0 mmol, 2.0 equiv.). The Schlenk flask was evacuated and backfilled with argon and charged with anhydrous 1,4-dioxane (2.0 mL). The reaction was stirred under argon at 80° C. and monitored by TLC. When the reaction was complete after 8 hours, the solvent was removed in vacuo and the reaction crude was purified by flash column chromatography (3% methanol in dichloromethane) to afford desired 2-(2,4-dimethoxyphenyl)-6-(4-methoxybenzylamino)-9-isopropylpurine (207 mg, 96%). 1H NMR (400 MHz, CDCl3) δ 1.59 (d, 6H, J=6.8 Hz), 3.79 (s, 3H), 3.84 (s, 3H), 3.85 (s, 3H), 4.87–4.96 (m, 3H), 6.14 (br, 1H), 6.57–6.60 (m, 2H), 6.85 (d, 2H, J=8.6 Hz), 7.34 (d, 2H, J=8.6 Hz), 7.73 (s, 1H), 7.78 (d, 1H, J=8.2 Hz); HRMS (MALDI-FTMS) [MH+] C24H28N5O3 434.2187, found: 434.2168.

Workup

  1. dry with materialBoronic Acid coupling reactions: A 10 mL flame-dried Schlenk flask
  2. customequipped with a magnetic stir bar
  3. customThe Schlenk flask was evacuated
  4. additioncharged with anhydrous 1,4-dioxane (2.0 mL)
  5. customthe solvent was removed in vacuo
  6. customthe reaction crude
  7. customwas purified by flash column chromatography (3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-02775c298ebf4f80b397e2c0c2663437
Source dataset
uspto-grants-2007_02
Patent number
US07176312B2

Reaction notes

Loading…