Diisopropylethylamine → (S)-N-(1-(7-fluoro-1-phenyl-1H-benzo[d]imidazol-2-yl)ethyl)-9H-purin-6-amine

HRID 243295Notes

Reaction equation

HRID 243295 reaction equation
[F:1][C:2]1[C:7]2[N:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:9]([C@@H:11]([NH2:13])[CH3:12])=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl[C:21]1[N:29]=[CH:28][N:27]=[C:26]2[C:22]=1[N:23]=[CH:24][NH:25]2.CCN(C(C)C)C(C)C>C(O)CCC>[F:1][C:2]1[C:7]2[N:8]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:9]([C@@H:11]([NH:13][C:21]3[N:29]=[CH:28][N:27]=[C:26]4[C:22]=3[N:23]=[CH:24][NH:25]4)[CH3:12])=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 68157214(S)-1-(7-Fluoro-1-phenyl-1H-benzo[D]imidazol-2-YL)ethanamineHCID 178478393HCID 178478393, compound

Product 1

HCID 178461919(S)-N-(1-(7-fluoro-1-phenyl-1H-benzo[d]imidazol-2-yl)ethyl)-9H-purin-6-amineYield 19.2%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-1-(7-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine from Example 7 (367 mg, 1.44 mmol), 6-chloro-9H-purine (222 mg, 1.44 mmol) and DIPEA (0.74 mL, 4.31 mmol) in n-butanol (3.5 mL) was stirred in a sealed tube for 48 h at 100° C. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated under reduced pressure. The product thus obtained was further purified by column chromatography (Si—PCC, gradient 0-20% 2M NH3/MeOH in EtOAc) followed by (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) and then sonicated in MeOH. The suspension was then diluted with diethyl ether and the solid collected by filtration affording 124 as a white solid (103 mg, 19%). LCMS: RT 3.40 min [M+H]+ 374.0. 1H NMR (DMSO, 400 MHz): δ 8.17-8.04 (2H, m), 7.98-7.86 (1H, br), 7.75-7.35 (6H, m), 7.19 (1H, td, J=8.09, 4.87 Hz), 7.02 (1H, dd, J=11.60, 8.02 Hz), 5.37 (1H, bs), 1.56 (3H, d, J=6.86 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customvolatiles were removed under reduced pressure
  3. washwas washed with MeOH
  4. washthe product eluted with 2M NH3/MeOH
  5. additionThe product containing fractions
  6. concentrationconcentrated under reduced pressure
  7. customThe product thus obtained
  8. customwas further purified by column chromatography (Si—PCC, gradient 0-20% 2M NH3/MeOH in EtOAc)
  9. customsonicated in MeOH
  10. additionThe suspension was then diluted with diethyl ether
  11. filtrationthe solid collected by filtration

Sources & evidence

ORD record
ord-949a2d0a7e424b71915896578b71472b
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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