Diisopropylethylamine → HCID 178463561, compound

HRID 243353Notes

Reaction equation

HRID 243353 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:12])[CH3:11])[N:7]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[C:6]=2[CH:19]=1.Cl[C:21]1[N:29]=[CH:28][N:27]=[C:26]2[C:22]=1[N:23]=[CH:24][N:25]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([CH:10]([NH:12][C:21]3[N:29]=[CH:28][N:27]=[C:26]4[C:22]=3[N:23]=[CH:24][NH:25]4)[CH3:11])[N:7]([C:13]3[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=3)[C:6]=2[CH:19]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68158079(S)-1-(6-Fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethylamine

Product 1

HCID 178463561HCID 178463561, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-1-(6-fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)ethylamine (81 mg, 0.32 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (83 mg, 0.35 mmol) and DIPEA (162 μL, 0.95 mmol) in n-butanol (1 mL) was heated at 90° C. in a sealed vial for 65 h. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue was loaded onto an Isolute® SCX-2 cartridge which and with MeOH followed by 2M NH3/MeOH (purification by SCX cartridge repeated three times). The product containing fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM) and then triturated with MeOH to afford 176 as an off-white solid (47 mg, 40%). LCMS (Method K): RT 2.75 min [M+H]+ 375.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.65 (1H, s), 8.79 (1H, d, J=2.46 Hz), 8.61 (1H, s), 8.15-7.91 (4H, m), 7.71 (1H, dd, J=8.80, 4.84 Hz), 7.55-7.46 (1H, m), 7.11 (1H, td, J=9.33, 2.43 Hz), 6.93 (1H, dd, J=8.91, 2.44 Hz), 5.49 (1H, s), 1.62 (3H, d, J=6.83 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customthe volatiles were removed under reduced pressure
  3. additionThe product containing fractions
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM)
  6. customtriturated with MeOH

Sources & evidence

ORD record
ord-726afe28c1bd4134ad6faf77b8b1f969
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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