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

HRID 1946166Notes

Reaction equation

HRID 1946166 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([O:26][CH3:27])[CH2:25][CH2:24][CH2:23][NH:22][CH2:21]4)[N:16]3[CH3:19])=[C:12]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[N:11]=2)[C:8]2[CH:34]=[CH:35][CH:36]=[CH:37][C:7]=2[N:6]=1)[CH3:4].[CH3:38][C:39]1([CH3:42])[CH2:41][O:40]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([O:26][CH3:27])[CH2:25][CH2:24][CH2:23][N:22]([CH2:38][C:39]([CH3:42])([OH:40])[CH3:41])[CH2:21]4)[N:16]3[CH3:19])=[C:12]([N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[N:11]=2)[C:8]2[CH:34]=[CH:35][CH:36]=[CH:37][C:7]=2[N:6]=1)[CH3:4]

Participants

5

Reactant 3

HCID 11208Isobutylene oxide2×HCID 81531DiisopropylethylamineHCID 674926392-(2-Ethylbenzoimidazol-1-yl)-8-(3-methoxypiperidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine dihydrochloride

Product 1

HCID 596060401-(3-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)-3-methoxypiperidin-1-yl)-2-methylpropan-2-olYield 34.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-(2-ethylbenzoimidazol-1-yl)-8-(3-methoxypiperidin-3-yl)-9-methyl-6-morpholin-4-yl-9H-purine dihydrochloride (150 mg, 0.27 mmol), 2,2-dimethyloxirane (242 μL, 2.73 mmol) and DIPEA (187 μL, 1.09 mmol) in MeCN (3 mL) was heated at 70° C. r.t. for 3 h before further 2,2-dimethyloxirane (242 μL, 2.73 mmol) was added and the mixture heated at 90° C. for 6 h. The reaction mixture was concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%) affording 791 (51 mg, 34%). LCMS (method I): RT 2.72 min, [M+H]+ 549.3. 1H NMR (DMSO, 400 MHz): δ 8.03-8.02 (1 H, m), 7.64-7.63 (1 H, m), 7.25-7.24 (2 H, m), 4.26 (4 H, brd s), 4.08 (1 H, s), 3.91 (3 H, s), 3.79 (4 H, t, J=4.72 Hz), 3.27-3.26 (2 H, m), 3.20-3.15 (1 H, m), 3.06 (3 H, s), 3.01-2.97 (1 H, m), 2.69-2.61 (1 H, m), 2.46-2.38 (1 H, m), 2.25 (2 H, s), 2.17-2.14 (1 H, m), 1.92-1.75 (3 H, m), 1.33 (3 H, t, J=7.43 Hz), 1.03 (3 H, s), 0.94 (3 H, s)

Workup

  1. additionwas added
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe resulting residue purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)

Sources & evidence

ORD record
ord-f65a2af241ce451185ed9cab26f871a8
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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