Diisopropylethylamine → HCID 68158176, compound

HRID 243350Notes

Reaction equation

HRID 243350 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:14])[CH2:11][O:12][CH3:13])[N:7]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:6]=2[CH:21]=1.Cl[C:23]1[N:31]=[CH:30][N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][N:27]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:14][C:23]3[N:31]=[CH:30][N:29]=[C:28]4[C:24]=3[NH:25][CH:26]=[N:27]4)[CH2:11][O:12][CH3:13])[N:7]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:6]=2[CH:21]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157280HCID 68157280, compound

Product 1

HCID 68158176HCID 68158176, compoundYield 32.4%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (R)-1-(6-fluoro-1-phenyl-1H-benzoimidazol-2-yl)-2-methoxyethylamine (110 mg, 0.39 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (93 mg, 0.39 mmol) and DIPEA (340 mL, 1.9 mmol) in n-butanol (2.5 mL) was heated at 90° C. in a sealed vial for 18 h. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue was 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 0-10% 2M NH3/MeOH in DCM) to afford 171 as a white solid (51 mg, 32%). LCMS (Method B): RT 3.52 min [M+H]+ 404.0. 1H NMR (DMSO-d6, 400 MHz): δ 8.25-8.01 (2H, m), 7.87 (1H, s), 7.77-7.47 (6H, m), 7.15-7.05 (1H, m), 6.87 (1H, dd, J=8.93, 2.37 Hz), 5.64 (1H, s), 3.84 (2H, d, J=6.60 Hz), 3.14 (3H, s). Signals split due to presence of rotamers/tautomers

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 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-a857d7679ea548cbb6cfc876669d229a
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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