Potassium Carbonate → HCID 90402801, compound

HRID 2200729Notes

Reaction equation

HRID 2200729 reaction equation
[Cl:1][C:2]1[CH:32]=[CH:31][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[NH:13][C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:29])[F:28])[CH:21]=2)=[CH:4][CH:3]=1.Br[CH2:34][CH2:35][CH2:36][N:37]1[C:45](=[O:46])[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]1=[O:47].C(=O)([O-])[O-].[K+].[K+]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]2[C:15]3[C:14](=[O:16])[N:13]([CH2:34][CH2:35][CH2:36][N:37]4[C:45](=[O:46])[C:44]5[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=5)[C:38]4=[O:47])[C:12](=[O:17])[N:11]([CH3:18])[C:10]=3[N:9]=[C:8]2[O:19][C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([O:26][C:27]([F:30])([F:28])[F:29])[CH:21]=2)=[CH:31][CH:32]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 21611N-3-BromopropylphthalimideHCID 90403003HCID 90403003, compound2×

Product 1

HCID 90402801HCID 90402801, compoundYield 100%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Step 1 7-(4-Chlorobenzyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (1.0 g, 2.14 mmol, intermediate 9), 2-(3-bromopropyl)isoindoline-1,3-dione (0.63 g, 2.36 mmol), potassium carbonate (0.44 g, 3.21 mmol) and TBAI (0.040 g) were combined in DMF (20 mL) and heated at 100° C. for 3 h. The reaction was cooled to room temperature, diluted with water (200 mL) and extracted with ethyl acetate (3×100 mL). The combined organic extracts were washed with 1N lithium chloride (2×100 mL), dried with magnesium sulfate, filtered and the solvent removed under reduced pressure to give a clear oil. The oil was purified using an 80 g silica gel flash column eluted with a gradient of 25% to 50% ethyl acetate/hexanes to give 7-(4-chlorobenzyl)-1-(3-(1,3-dioxoisoindolin-2-yl)propyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (1.4 g, 100% yield) as a white solid. LCMS retention time=4.660 minutes and 100% purity, LCMS MH+ 654. 1H NMR (CDCl3) δ 7.78-7.83 (m, 2H), 7.65-7.70 (m, 2H), 7.41 (t, 1H, J=8 Hz), 7.32 (dd, 4H, J=12 Hz and 28 Hz), 7.10-7.23 (m, 4H), 5.35 (s, 2H), 4.05-4.14 (m, 2H), 3.76 (t, 2H, J=8 Hz), 3.38 (s, 3H), 2.01-2.11 (m, 2H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe combined organic extracts were washed with 1N lithium chloride (2×100 mL)
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customto give a clear oil
  8. customThe oil was purified
  9. washeluted with a gradient of 25% to 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-032aa60db9d5429aac263b202659d8ad
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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