Isobutylene oxide → 3-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-1-(2-hydroxy-2-methylpropyl)piperidin-3-ol

HRID 1946150Notes

Reaction equation

HRID 1946150 reaction equation
Cl.Cl.[CH2:3]([C:5]1[N:9]([C:10]2[N:18]=[C:17]3[C:13]([N:14]=[C:15]([C:20]4([OH:26])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21]4)[N:16]3[CH3:19])=[C:12]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)[N:11]=2)[C:8]2[CH:33]=[CH:34][CH:35]=[CH:36][C:7]=2[N:6]=1)[CH3:4].[CH3:37][C:38]1([CH3:41])[CH2:40][O:39]1.CCN(C(C)C)C(C)C>CC#N>[CH2:3]([C:5]1[N:9]([C:10]2[N:18]=[C:17]3[C:13]([N:14]=[C:15]([C:20]4([OH:26])[CH2:25][CH2:24][CH2:23][N:22]([CH2:37][C:38]([OH:39])([CH3:41])[CH3:40])[CH2:21]4)[N:16]3[CH3:19])=[C:12]([N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[N:11]=2)[C:8]2[CH:33]=[CH:34][CH:35]=[CH:36][C:7]=2[N:6]=1)[CH3:4]

Participants

5

Reactant 3

HCID 11208Isobutylene oxideHCID 81531DiisopropylethylamineHCID 674921803-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-3-ol dihydrochloride

Product 1

HCID 596058943-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-1-(2-hydroxy-2-methylpropyl)piperidin-3-olYield 23.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3-[2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-3-ol dihydrochloride (150 mg, 0.28 mmol), 2,2-dimethyloxirane (100 μL, 1.12 mmol) and DIPEA (192 μL, 1.12 mmol) in MeCN (4 mL) was stirred at r.t. for 20 h then heated at 70° C. for 24 h. The reaction mixture was concentrated in vacuo and the resulting residue purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 5-30%) affording 746 (35 mg, 23%). LCMS (method I): RT 2.57 min, [M+H]+ 535.2. 1H NMR (DMSO, 400 MHz): δ 8.03-7.98 (1 H, m), 7.65-7.61 (1 H, m), 7.28-7.21 (2 H, m), 5.46 (1 H, s), 4.45-4.05 (5 H, m), 3.96 (3 H, s), 3.77-3.76 (4 H, m), 3.30-3.22 (2 H, m), 3.07-2.99 (1 H, m), 2.91-2.83 (1 H, m), 2.70-2.60 (1 H, m), 2.45-2.35 (1 H, m), 2.26 (2 H, s), 2.15-2.00 (1 H, m), 1.96-1.69 (3 H, m), 1.32 (3 H, t, J=7.43 Hz), 1.01 (6 H, d, J=15.78 Hz)

Workup

  1. temperaturethen heated at 70° C. for 24 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe resulting residue purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 5-30%)

Sources & evidence

ORD record
ord-66aa3b9874fe49d0909f5d5fcf437092
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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