Diisopropylethylamine → HCID 178456862, compound

HRID 243377Notes

Reaction equation

HRID 243377 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:13])[CH2:11][CH3:12])[N:7]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)[C:6]=2[CH:20]=1.Cl[C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[N:24]=[CH:25][N:26]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:13][C:22]3[N:30]=[CH:29][N:28]=[C:27]4[C:23]=3[N:24]=[CH:25][NH:26]4)[CH2:11][CH3:12])[N:7]([C:14]3[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=3)[C:6]=2[CH:20]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157916HCID 68157916, compound

Product 1

HCID 178456862HCID 178456862, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-1-(6-fluoro-1-pyridin-3-yl-1H-benzoimidazol-2-yl)propylamine (243 mg, 0.90 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (210 mg, 0.90 mmol) and DIPEA (780 μL, 4.5 mmol) in n-butanol (3 mL) was heated at 100° C. in a sealed vial for 18 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 0-10% 2M NH3/MeOH in DCM) to afford 205 (145 mg, 42%). LCMS (Method K): RT 2.96 min [M+H]+ 389.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.65 (1H, s), 8.81 (1H, d, J=2.47 Hz), 8.67 (1H, br s), 8.21-8.01 (3H, m), 7.91 (1H, br s), 7.73 (1H, dd, J=8.81, 4.84 Hz), 7.56 (1H, br s), 7.18-7.08 (1H, m), 6.95 (1H, dd, J=8.88, 2.48 Hz), 5.35 (1H, br s), 2.19-2.01 (2H, m), 0.90 (3H, t, J=7.32 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 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-77005edba7074ed9a8882b1b02fc1b69
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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