Sulfuric Acid → 2-(4-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)piperidin-1-yl)-2-methylpropanamide

HRID 1923311Notes

Reaction equation

HRID 1923311 reaction equation
[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH:18]4[CH2:23][CH2:22][N:21]([C:24]([CH3:28])([CH3:27])[C:25]#[N:26])[CH2:20][CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)[N:9]=2)[C:6]2[CH:35]=[CH:36][CH:37]=[CH:38][C:5]=2[N:4]=1)[CH3:2].[OH:39]S(O)(=O)=O.C([O-])([O-])=O.[K+].[K+]>>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH:18]4[CH2:23][CH2:22][N:21]([C:24]([CH3:28])([CH3:27])[C:25]([NH2:26])=[O:39])[CH2:20][CH2:19]4)[N:14]3[CH3:17])=[C:10]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)[N:9]=2)[C:6]2[CH:35]=[CH:36][CH:37]=[CH:38][C:5]=2[N:4]=1)[CH3:2]

Participants

4

Reactant 3

HCID 1118Sulfuric AcidHCID 11430Potassium CarbonateHCID 596055752-{4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-1-yl}-2-methylpropionitrile

Product 1

HCID 596060092-(4-(2-(2-ethyl-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)piperidin-1-yl)-2-methylpropanamide

Procedure

2-{4-[2-(2-Ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purin-8-yl]piperidin-1-yl}-2-methylpropionitrile (300 mg, 0.58 mmol) was added slowly to conc. H2SO4 (3.5 mL) The resulting mixture was allowed to stir at r.t. for 3 h then poured onto ice and basified with K2CO3. The resulting mixture was extracted with DCM and the combined organic phases dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%) then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH affording 703 (177 mg, 57%). LCMS (method I): RT 2.45 min, [M+H]+ 532.3. 1H NMR (DMSO, 400 MHz): δ 8.01-7.97 (1 H, m), 7.63-7.62 (1 H, m), 7.23-7.22 (3 H, m), 6.93 (1 H, d, J=3.36 Hz), 4.26 (4 H, brd s), 3.79-3.74 (7 H, m), 3.26 (2 H, q, J=7.42 Hz), 3.07-2.97 (1 H, m), 2.88 (2 H, d, J=10.76 Hz), 2.32-2.21 (2 H, m), 1.93-1.91 (4 H, m), 1.33 (3 H, t, J=7.44 Hz), 1.12 (6 H, s)

Workup

  1. extractionThe resulting mixture was extracted with DCM
  2. dry with materialthe combined organic phases dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%)
  5. washwas washed with MeOH
  6. washthe product eluted with 2M NH3/MeOH affording 703 (177 mg, 57%)
  7. customRT 2.45 min, [M+H]+ 532.3

Sources & evidence

ORD record
ord-f18479051d884dac94fd948e226b62eb
Source dataset
uspto-grants-2012_05
Patent number
US08173650B2

Reaction notes

Loading…