Diisopropylethylamine → HCID 178463576, compound

HRID 243383Notes

Reaction equation

HRID 243383 reaction equation
[C:1]1([N:7]2[C:11]3[CH:12]=[N:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[CH:16]([NH2:18])[CH3:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:20]1[N:28]=[CH:27][N:26]=[C:25]2[C:21]=1[N:22]=[CH:23][N:24]2C1CCCCO1.CCN(C(C)C)C(C)C.Cl.O1CCOCC1>C(O)CCC>[C:1]1([N:7]2[C:11]3[CH:12]=[N:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[CH:16]([NH:18][C:20]2[N:28]=[CH:27][N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][NH:24]3)[CH3:17])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 204431481,4-Dioxane hydrochlorideHCID 681579831-(3-Phenyl-3H-imidazo[4,5-c]pyridin-2-yl)ethylamine

Product 1

HCID 178463576HCID 178463576, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1-(3-phenyl-3H-imidazo[4,5-c]pyridin-2-yl)ethylamine (254 mg, 1.07 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (0.35 g, 1.49 mmol) and DIPEA (0.34 mL, 1.92 mmol) in 1-butanol (3 mL) was stirred at 90° C. in a sealed tube for 16 h. The resulting mixture was concentrated in vacuo and residue was purified by chromatography (SiO2 0-10% (2M ammonia in methanol) in DCM). The product was dissolved in methanol and treated with HCl/dioxane (4M, 1.3 mL, 5.35 mmol) and stirred for 20 minutes. The mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH and the product eluted with 2M NH3/MeOH then concentrated in vacuo. The resulting residue was purified by chromatography (SiO2, 0-15% (2M ammonia in methanol) in DCM) to give a waxy solid which was triturated with EtOAc/diethyl ether to give 237 as a brown solid (0.056 g, 15%). LCMS (method K): Rt 1.98 min, [M+H]+ 357. 1H NMR (DMSO-d6): δ 13.10-12.60 (1H, bs), 8.43 (1H, s), 8.37 (1H, d, J=5.53 Hz), 8.13 (1H, s), 8.07 (1H, s), 7.70-7.68 (3H, m), 7.61-7.50 (3H, m), 5.49 (1H, m), 1.59 (3H, d, J=6.87 Hz)

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo and residue
  2. customwas purified by chromatography (SiO2 0-10% (2M ammonia in methanol) in DCM)
  3. dissolutionThe product was dissolved in methanol
  4. stirringstirred for 20 minutes
  5. washwashed with MeOH
  6. washthe product eluted with 2M NH3/MeOH
  7. concentrationthen concentrated in vacuo
  8. customThe resulting residue was purified by chromatography (SiO2, 0-15% (2M ammonia in methanol) in DCM)
  9. customto give a waxy solid which
  10. customwas triturated with EtOAc/diethyl ether

Sources & evidence

ORD record
ord-0ad4955626f94b63a209484daa396d0b
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

Loading…