Diisopropylethylamine → HCID 178461937, compound

HRID 243491Notes

Reaction equation

HRID 243491 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[N:14]([CH3:18])[N:15]=[CH:16][CH:17]=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.Cl.O1CCOCC1>CC(O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H: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[N:14]([CH3:18])[N:15]=[CH:16][CH:17]=3)[C:6]=2[CH:19]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 204431481,4-Dioxane hydrochlorideHCID 68158163HCID 68158163, compound

Product 1

HCID 178461937HCID 178461937, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-1-[6-fluoro-1-(2-methyl-2H-pyrazol-3-yl)-1H-benzoimidazol-2-yl]-ethylamine, (0.093 g, 0.36 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (0.119 g, 0.50 mmol) and DIPEA (0.12 mL, 0.65 mmol) in IPA (2 mL) was stirred at 80° C. in a sealed tube for 16 h. After cooling, the reaction mixture was concentrated in vacuo and the residue purified by chromatography (SiO2, 0-8% (2M ammonia in methanol) in DCM). The product was dissolved in methanol (4 mL) and treated with HCl/dioxane (4M, 0.6 mL, 2.4 mmol) then stirred for 30 minutes. The resulting mixture was concentrated in vacuo and residue loaded onto an Isolute® SCX-2 cartridge and washed with MeOH. The product was eluted with 2M NH3/MeOH then concentrated in vacuo to give 417 as a white solid (0.078 g, 58%). LCMS (Method K): RT 2.79, 2.95 min [M+H]+ 378.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.91-12.00 (1H, m), 8.30-7.81 (3H, m), 7.78-7.71 (1H, m), 7.50 (1H, s), 7.23-7.03 (1H, m), 7.03-6.92 (1H, m), 6.69-6.51 (1H, m), 5.60-5.22 (1H, m), 3.62-3.55 (3H, m), 1.65-1.54 (3H, m). Signals split due to presence of rotamers/tautomers

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customthe residue purified by chromatography (SiO2, 0-8% (2M ammonia in methanol) in DCM)
  4. dissolutionThe product was dissolved in methanol (4 mL)
  5. stirringthen stirred for 30 minutes
  6. concentrationThe resulting mixture was concentrated in vacuo and residue
  7. washwashed with MeOH
  8. washThe product was eluted with 2M NH3/MeOH
  9. concentrationthen concentrated in vacuo

Sources & evidence

ORD record
ord-49506fc2b6124f73ba9a89b0ece68e41
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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