P-Anisidine → 2-(4-Methoxyphenylamino)-6-(4-methoxybenzylamino)-9-isopropylpurine

HRID 348391Notes

Reaction equation

HRID 348391 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:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1.CC([O-])(C)C.[K+]>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:32]=[CH:31][C:29]([NH:30][C:2]2[N:10]=[C:9]3[C:5]([N:6]=[CH:7][N:8]3[CH:11]([CH3:13])[CH3:12])=[C:4]([NH:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[N:3]=2)=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 7732P-AnisidineHCID 98587852-Chloro-9-isopropyl-N-(4-methoxybenzyl)-9H-purin-6-amineHCID 23665647Potassium tert-butoxide

Product 1

HCID 101589932-(4-Methoxyphenylamino)-6-(4-methoxybenzylamino)-9-isopropylpurineYield 97%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

Aniline coupling: 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), 4-methoxyaniline (0.092 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 KOtBu (0.112 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-(4-methoxyphenylamino)-6-(4-methoxybenzylamino)-9-isopropylpurine (203 mg, 97%): 1H NMR (500 MHz, CDCl3) δ 1.54 (d, 6H, J=6.6 Hz), 3.76 (s, 3H), 3.78 (s, 3H), 4.66 (m, 1H, J=6.6 Hz), 4.72 (br, 2H), 6.06 (br, 1H), 6.60 (br, 1H), 6.82 (d, 2H, J=13 Hz), 6.84 (d, 2H, J=13 Hz), 7.09 (s, 1H), 7.26 (d, 2H, J=8.8 Hz), 7.42 (s, 1H), 7.56 (d, 2H, J=8.8 Hz); HRMS (MALDI-FTMS) [MH+] C23H27N6O2 419.2195, found: 419.2209.

Workup

  1. dry with materialAniline coupling: 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-8e67d242167543a98ae09d64f5fe1082
Source dataset
uspto-grants-2007_02
Patent number
US07176312B2

Reaction notes

Loading…