Diisopropylethylamine → HCID 178461943, compound

HRID 243493Notes

Reaction equation

HRID 243493 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][N:16]([CH3:18])[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[CH:14]=[N:15][N:16]([CH3:18])[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 68157529(S)-1-[6-Fluoro-1-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]ethylamine

Product 1

HCID 178461943HCID 178461943, compoundYield 63.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-1-[6-fluoro-1-(1-methyl-1H-pyrazol-4-yl)-1H-benzoimidazol-2-yl]ethylamine, (0.055 g, 0.21 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (0.070 g, 0.30 mmol) and DIPEA (0.07 mL, 0.38 mmol) in IPA (1.5 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, 0-10% (2M ammonia in methanol) in DCM). The product was dissolved in methanol (4 mL) and treated with HCl/dioxane (4M, 0.5 mL, 2.0 mmol) then stirred for 15 minutes. The resulting mixture was concentrated in vacuo and the residue loaded onto an Isolute® SCX-2 cartridge and washed with MeOH then the product eluted with 2M NH3/MeOH and concentrated in vacuo to give 419 as a white solid (0.050 g, 63%). LCMS (Method K): RT 2.65 min [M+H]+ 378.0. 1H NMR (DMSO-d6, 400 MHz): δ 12.90 (1H, s), 8.22-8.03 (3H, m), 7.89-7.81 (1H, m), 7.76 (1H, s), 7.66-7.62 (1H, m), 7.09-7.05 (1H, m), 7.00-6.91 (1H, m), 5.61-5.42 (1H, m), 3.86 (3H, s), 1.57 (3H, d, J=6.84 Hz)

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. customthe residue purified by chromatography (SiO2, 0-10% (2M ammonia in methanol) in DCM)
  4. dissolutionThe product was dissolved in methanol (4 mL)
  5. stirringthen stirred for 15 minutes
  6. concentrationThe resulting mixture was concentrated in vacuo
  7. washwashed with MeOH
  8. washthe product eluted with 2M NH3/MeOH
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9f01b4ba846041c2bff61c6ac7e225a2
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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