Potassium Carbonate → HCID 67492783, compound

HRID 1945947Notes

Reaction equation

HRID 1945947 reaction equation
[CH2:1]([O:3][C:4](=[O:9])[C:5](Br)([CH3:7])[CH3:6])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[C@H:16]12[CH2:22][C@H:19]([NH:20][CH2:21]1)[CH2:18][N:17]2[CH2:23][C:24]1[N:25]([CH3:50])[C:26]2[C:31]([N:32]=1)=[C:30]([N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1)[N:29]=[C:28]([N:39]1[C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=3[N:41]=[C:40]1[CH2:48][CH3:49])[N:27]=2>C(#N)C>[CH2:48]([C:40]1[N:39]([C:28]2[N:27]=[C:26]3[C:31]([N:32]=[C:24]([CH2:23][N:17]4[CH2:18][C@@H:19]5[CH2:22][C@H:16]4[CH2:21][N:20]5[C:5]([CH3:7])([CH3:6])[C:4]([O:3][CH2:1][CH3:2])=[O:9])[N:25]3[CH3:50])=[C:30]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)[N:29]=2)[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][C:42]=2[N:41]=1)[CH3:49]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 11745Propanoic acid, 2-bromo-2-methyl-, ethyl esterHCID 67492183HCID 67492183, compound

Product 1

HCID 67492783HCID 67492783, compoundYield 58%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

2-Bromo-2-methylpropionic acid ethyl ester (90 μL, 0.61 mmol) was added to a solution of potassium carbonate (84 mg, 0.61 mmol) and 8-[(1S,4S)-1-(2,5-diazabicyclo[2.2.1]hept-2-yl)methyl]-2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine (140 mg, 0.30 mmol) in anhydrous acetonitrile. The resulting mixture was heated at 80° C. for 48 h, then cooled to ambient temperature and partitioned between EtOAc and water. The organic layer was separated, washed with brine, then dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; gradient from 100:0 to 85:15) to afford 417 as a cream solid (100 mg, 58%). LCMS (Method I): RT=2.92 min, M+H+=588. 1H NMR (CDCl3, 400 MHz) δ 8.01 (m, 1 H); 7.75 (m, 1 H); 7.29-7.23 (m, 2 H); 4.34 (m, 4 H); 4.15 (m, 2 H); 3.93-3.82 (m, 9 H); 3.64 (m, 1 H); 3.35 (q, J=7.5 Hz, 2 H); 3.19 (m, 1 H); 2.81-2.63 (m, 3 H); 1.58 (m, 4 H); 1.45 (t, J=7.5 Hz, 3 H); 1.36 (m, 2 H) and 1.32-1.23 (m, 6 H)

Workup

  1. temperaturecooled to ambient temperature
  2. custompartitioned between EtOAc and water
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by flash chromatography (Si—PPC, DCM:MeOH; gradient from 100:0 to 85:15)

Sources & evidence

ORD record
ord-e166bba668f34f4da4f9ae4b44f1c0dd
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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