Diisopropylethylamine → [1-(1-Phenyl-1H-imidazo[4,5-b]pyridin-2-yl)-ethyl]-(9H-purin-6-yl)-amine

HRID 243371Notes

Reaction equation

HRID 243371 reaction equation
[C:1]1([N:7]2[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]=[C:8]2[C@@H: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>C(O)CCC>[C:1]1([N:7]2[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=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

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157105(S)-1-(1-Phenyl-1H-imidazo[4,5-b]pyridin-2-yl)ethylamine

Product 1

HCID 178463578[1-(1-Phenyl-1H-imidazo[4,5-b]pyridin-2-yl)-ethyl]-(9H-purin-6-yl)-amineYield 36.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-1-(1-phenyl-1H-imidazo[4,5-b]pyridin-2-yl)ethylamine (330 mg, 1.38 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (460 mg, 1.94 mmol) and DIPEA (440 μL, 2.49 mmol) in n-butanol (2 mL) was heated at 90° C. in a sealed vial for 16 h. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue loaded onto an Isolute® SCX-2 cartridge and washed with MeOH followed by 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM) and then crystallised from EtOAc and MeOH to afford 199 as a white solid (178 mg, 36%). LCMS (Method K): RT 2.72 min [M+H]+ 357.0. 1H NMR (DMSO-d6, 400 MHz): δ 8.42 (1H, dd, J=4.73, 1.53 Hz), 8.20-7.94 (3H, m), 7.68 (2H, d, J=7.55 Hz), 7.63-7.48 (4H, m), 7.23 (1H, dd, J=8.06, 4.74 Hz), 5.51 (1H, br s), 1.60 (3H, d, J=6.85 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customthe volatiles were removed under reduced pressure
  3. washwashed with MeOH
  4. additionThe product containing fractions
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-15% 2M NH3/MeOH in DCM)
  7. customcrystallised from EtOAc and MeOH

Sources & evidence

ORD record
ord-b224b2f137cd474f88ca846b3589d237
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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