Acetonitrile → HCID 67776765, compound

HRID 511567Notes

Reaction equation

HRID 511567 reaction equation
[CH3:1][O:2][C:3]1[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[CH:39][C:4]=1[CH2:5][NH:6][C:7]1[N:15]=[CH:14][N:13]=[C:12]2[C:8]=1[N:9]=[CH:10][N:11]2[C@H:16]1[C@@H:20]2[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]2[C@@H:18]([CH2:26][NH:27][CH:28]2[CH2:31][CH:30]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:29]2)[CH2:17]1.C(#N)C.[CH:48](I)([CH3:50])[CH3:49]>C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[CH:39][C:4]=1[CH2:5][NH:6][C:7]1[N:15]=[CH:14][N:13]=[C:12]2[C:8]=1[N:9]=[CH:10][N:11]2[C@H:16]1[C@@H:20]2[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]2[C@@H:18]([CH2:26][N:27]([CH:48]([CH3:50])[CH3:49])[CH:28]2[CH2:29][CH:30]([CH2:32][CH2:33][C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH2:31]2)[CH2:17]1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 6362Isopropyl iodide3×HCID 67774676HCID 67774676, compound

Product 1

HCID 67776765HCID 67776765, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent3×

Conditions

Temperature
80 °C

Procedure

Ethyl 3-(3-((((3aR,4R,6R,6aS)-6-(6-((2,4-dimethoxybenzyl)amino)-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)amino)cyclobutyl)propanoate (0.06 g, 0.1 mmol) was taken up in acetonitrile (2.6 mL, 50 mmol) and isopropyl iodide (0.098 mL, 0.98 mmol) and triethylamine (0.21 mL, 1.5 mmol) were added. The reaction was heated to 80° C. for 12 hours at which point the reaction appeared to stall. Another 15 equivalents triethylamine and another 15 equivalents isopropyl iodide were added and the reaction continued 8 hours more. Reaction appeared to have stalled again so another 15 equivalents each of isopropyl iodide and triethylamine were added. Upon consumption of the starting material the reaction was concentrated and saturated Na2CO3 (20 mls) and DCM (20 mls) was added. The residue was partitioned between the organic layer and the aqueous layer. The aqueous layer was extracted 3 times with DCM, then the combined organics were dried and purified by FC (DCM/7N NH3 in MeOH 97:3). Product was still contaminated with TEA-H+I—, so to a 30 ml solution of the product in DCM was added 20 mls saturated NaHCO3 and 10 mls 1N NaOH. The mixture was stirred for 15 minutes then the aqueous was extracted with DCM 3 times. The combined organics were dried with MgSO4 and solvent removed to yield pure ethyl 3-(3-((((3aR,4R,6R,6aS)-6-(6-((2,4-dimethoxybenzyl)amino)-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)cyclobutyl)propanoate (0.045 g; 70%) as a brown foam/solid with no more amine salts present by NMR. MS (ESI+) for C35H50N6O6 m/z 651.3 [M+H]+.

Workup

  1. customReaction
  2. additionwere added
  3. customUpon consumption of the starting material the reaction
  4. concentrationwas concentrated
  5. additionsaturated Na2CO3 (20 mls) and DCM (20 mls) was added
  6. customThe residue was partitioned between the organic layer
  7. extractionThe aqueous layer was extracted 3 times with DCM
  8. customthe combined organics were dried
  9. custompurified by FC (DCM/7N NH3 in MeOH 97:3)
  10. additionwas added 20 mls saturated NaHCO3 and 10 mls 1N NaOH
  11. extractionthe aqueous was extracted with DCM 3 times
  12. dry with materialThe combined organics were dried with MgSO4 and solvent
  13. customremoved

Sources & evidence

ORD record
ord-db44a460ca0d4620bd54f4979a7cd41b
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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