Diisopropylethylamine → HCID 178461957, compound

HRID 243285Notes

Reaction equation

HRID 243285 reaction equation
[C:1]1([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=[C:8]2[C@@H:16]([NH2:18])[CH3:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:20]1[N:28]=[CH:27][N:26]=[C:25]2[C:21]=1[N:22]=[CH:23][NH:24]2.CCN(C(C)C)C(C)C>C(O)CCC>[C:1]1([N:7]2[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=[C:8]2[C@@H:16]([NH:18][C:20]2[N:28]=[CH:27][N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][NH:24]3)[CH3:17])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 68157412HCID 68157412, compoundHCID 178478393HCID 178478393, compound

Product 1

HCID 178461957HCID 178461957, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-1-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)ethylamine from Example 10 (270 mg, 1.13 mmol), 6-chloro-9H-purine (250 mg, 1.59 mmol) and DIPEA (0.36 mL, 2.04 mmol) in n-butanol (1.5 mL) was stirred in a sealed tube for 48 h at 120° C. After cooling to RT, the crude reaction mixture was partitioned between DCM and a saturated solution of NaHCO3. The aqueous phase was further extracted with DCM (×3) and the combined organic layers were washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM), then triturated with diethyl ether and then submitted to preparative HPLC (Phenomenex Gemini 5 μm C18 on a 60 min gradient 20-98% 0.1% HCO2H in acetonitrile/water) affording 114 as an off-white solid (32 mg, 8%). LCMS: RT 2.64 min [M+H]+ 357.0. 1H NMR (DMSO, 400 MHz): δ 8.23 (1H, dd, J=4.76, 1.48 Hz), 8.18-7.97 (4H, m), 7.67-7.41 (5H, m), 7.29 (1H, dd, J=7.99, 4.76 Hz), 1.57 (3H, d, J=6.83 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customthe crude reaction mixture
  3. customwas partitioned between DCM
  4. extractionThe aqueous phase was further extracted with DCM (×3)
  5. washthe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)
  9. customtriturated with diethyl ether
  10. customC18 on a 60 min gradient 20-98% 0.1% HCO2H in acetonitrile/water

Sources & evidence

ORD record
ord-a22943fca91c4ae9960a875027dba795
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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