Diisopropylethylamine → HCID 178456070, compound

HRID 243386Notes

Reaction equation

HRID 243386 reaction equation
[NH2:1][C@H:2]([C:5]1[N:6]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:7]2[C:13]([C:14]#[N:15])=[C:12]([F:16])[CH:11]=[CH:10][C:8]=2[N:9]=1)[CH2:3][CH3:4].Cl[C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[N:26]=[CH:27][N:28]2C1CCCCO1.CCN(C(C)C)C(C)C.Cl.O1CCOCC1>CC(O)C>[F:16][C:12]1[CH:11]=[CH:10][C:8]2[N:9]=[C:5]([C@@H:2]([NH:1][C:24]3[N:32]=[CH:31][N:30]=[C:29]4[C:25]=3[N:26]=[CH:27][NH:28]4)[CH2:3][CH3:4])[N:6]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:7]=2[C:13]=1[C:14]#[N:15]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 204431481,4-Dioxane hydrochlorideHCID 681574452-((S)-1-Amino-propyl)-5-fluoro-3-phenyl-3H-benzoimidazole-4-carbonitrile

Product 1

HCID 178456070HCID 178456070, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-((S)-1-amino-propyl)-5-fluoro-3-phenyl-3H-benzoimidazole-4-carbonitrile (0.260 g, 0.88 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (0.290 g, 1.24 mmol) and DIPEA (0.28 mL, 1.59 m mol) in IPA (2 mL) was stirred at 90° C. in a sealed tube for 16 h. The resulting 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 and treated with HCl/dioxane (4M, 1.1 mL, 0.00450 mol) and stirred for 20 minutes. The mixture was loaded onto an Isolute® SCX-2 cartridge, washed with MeOH and the product eluted with 2M NH3/MeOH then concentrated in vacuo. The resulting residue was purified by chromatography (SiO2, 0-10% (2M ammonia in methanol) in DCM) to give 244 as a white solid (0.205 g, 57%). LCMS (method K): Rt 3.51 min, [M+H]+ 413. 1H NMR (DMSO-d6): δ 13.20-12.50 (1H, bs), 9.60 (1H, s), 8.00 (1H, s), 7.71 (1H, m), 7.60 (2H, s), 7.51-7.49 (3H, m), 7.11-7.08 (1H, m), 6.86 (1H, m), 5.64 (1H, m), 2.10 (3H, s), 1.50 (3H, d, J=6.81 Hz)

Workup

  1. concentrationThe resulting mixture was concentrated in vacuo
  2. customthe residue purified by chromatography (SiO2 0-10% (2M ammonia in methanol) in DCM)
  3. dissolutionThe product was dissolved in methanol
  4. stirringstirred for 20 minutes
  5. washwashed with MeOH
  6. washthe product eluted with 2M NH3/MeOH
  7. concentrationthen concentrated in vacuo
  8. customThe resulting residue was purified by chromatography (SiO2, 0-10% (2M ammonia in methanol) in DCM)

Sources & evidence

ORD record
ord-a3e87f85b5ee41fb9a89ad57da731664
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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