Diisopropylethylamine → HCID 178467930, compound

HRID 243372Notes

Reaction equation

HRID 243372 reaction equation
[CH2:1]([O:3][CH2:4][C@H:5]([NH2:22])[C:6]1[N:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:9]2[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:8]=2[N:7]=1)[CH3:2].Cl[C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[N:26]=[CH:27][N:28]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[CH2:1]([O:3][CH2:4][CH:5]([NH:22][C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[N:26]=[CH:27][NH:28]2)[C:6]1[N:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:9]2[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:8]=2[N:7]=1)[CH3:2]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157555HCID 68157555, compound

Product 1

HCID 178467930HCID 178467930, compoundYield 22.3%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (R)-2-ethoxy-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine (510 mg, 1.7 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (410 mg, 1.7 mmol) and DIPEA (1.5 mL, 8.5 mmol) in n-butanol (6 mL) was heated at 90° C. for 18 h in a sealed vial. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH followed by 2M NH3/MeOH. The basic fractions were combined, concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) to afford 200 as a white solid (158 mg, 22%). LCMS (Method K): RT 3.80 min [M+H]+ 418.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.60 (1H, s), δ 8.22-8.05 (2H, m), 7.87 (1H, br s), 7.75-7.49 (6H, m), 7.11 (1H, td, J=9.32, 2.48 Hz), 6.89 (1H, dd, J=8.92, 2.50 Hz), 5.63 (1H, br s), 3.88 (2H, br d, J=6.76 Hz), 3.40-3.33 (2H, m), 1.01-0.91 (3H, m)

Workup

  1. temperatureAfter cooling to RT
  2. customthe volatiles were removed under reduced pressure
  3. washThe cartridge was washed with MeOH
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-795b9ef4942a4196baba5a1e68974aef
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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