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

HRID 1946187Notes

Reaction equation

HRID 1946187 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]4([F:22])[CH2:21][NH:20][CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[CH:32][C:5]=2[N:4]=1)[CH3:2].[CH3:33][C:34]1([CH3:37])[CH2:36][O:35]1>>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([C:18]4([F:22])[CH2:21][N:20]([CH2:33][C:34]([CH3:37])([OH:35])[CH3:36])[CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)[N:9]=2)[C:6]2[CH:29]=[CH:30][CH:31]=[CH:32][C:5]=2[N:4]=1)[CH3:2]

Participants

3

Reactant 2

HCID 11208Isobutylene oxideHCID 596055312-(2-ethylbenzoimidazol-1-yl)-8-(3-fluoroazetidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine

Product 1

HCID 596059751-(3-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-3-fluoroazetidin-1-yl)-2-methylpropan-2-olYield 21%

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-8-(3-fluoroazetidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine (90 mg, 0.21 mmol) and 2,2-dimethyloxirane (1 mL) in IMS (2 mL) was heated to 80° C. for 24 h then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-5%) then triturated with Et2O. The resulting residue was further purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 5-95%) affording 839 (22 mg, 21%). LCMS (method I): RT 2.63 min, [M+H]+ 509.3. 1H NMR (DMSO, 400 MHz): δ 8.04-8.03 (1 H, m), 7.65-7.62 (1 H, m), 7.26-7.25 (2 H, m), 4.28 (4 H, brd s), 4.14 (2 H, dd, J=18.78, 9.71 Hz), 3.82-3.74 (9 H, m), 3.31-3.29 (4 H, m), 1.34 (3 H, t, J=7.43 Hz), 1.07 (6 H, s)

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-5%)
  3. customthen triturated with Et2O
  4. customThe resulting residue was further purified by reverse phase HPLC (Phenomenex Gemini 5 μm C18, 0.1% HCO2H in water on a gradient acetonitrile 5-95%)

Sources & evidence

ORD record
ord-ef751f882d704db9af44b98d9228c87d
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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