1,4-Cyclohexadiene → 5-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)pentanoic acid

HRID 2284553Notes

Reaction equation

HRID 2284553 reaction equation
[CH3:1][O:2][C:3]1[CH:48]=[C:47]([O:49][CH3:50])[CH:46]=[CH:45][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:25])([CH3:24])[O:23][C@@H:19]4[C@@H:18]([CH2:26][N:27]([CH:42]([CH3:44])[CH3:43])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]([O:34]CC4C=CC=CC=4)=[O:33])[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.C1CC=CCC=1>C(O)C.[Pd]>[CH3:1][O:2][C:3]1[CH:48]=[C:47]([O:49][CH3:50])[CH:46]=[CH:45][C:4]=1[CH2:5][NH:6][C:7]1[C:8]2[CH:15]=[CH:14][N:13]([C@H:16]3[C@@H:20]4[O:21][C:22]([CH3:24])([CH3:25])[O:23][C@@H:19]4[C@@H:18]([CH2:26][N:27]([CH:42]([CH3:44])[CH3:43])[CH2:28][CH2:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1

Participants

5

Reactant 2

HCID 123431,4-CyclohexadieneHCID 67811594HCID 67811594, compound

Product 1

HCID 678172005-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)pentanoic acidYield 104%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
85 °C

Procedure

A solution of benzyl 5-((((3aR,4R,6R,6aR)-6-(4-((2,4-dimethoxybenzyl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(isopropyl)amino)pentanoate (151 mg, 0.220 mmol) in ethanol (4.1 mL) was treated with 10% palladium on carbon (51 mg, 0.048 mmol) and 1,4-cyclohexadiene (0.23 mL, 2.4 mmol). The mixture was heated at 85° C. until the starting material was consumed as indicated by HPLC. After about 1 h, the starting material was consumed as indicated by HPLC and the reaction mixture was cooled to room temperature. The mixture was filtered through a pad of celite and the pad was washed with 40 mL EtOH. The solution was concentrated to yield the title compound (136 mg, 104%) as a nearly colorless glass, which was taken up in toluene, concentrated and placed under high vac. The material was determined to be of sufficient purity to be used in the next step without purification: MS (ESI+) for C31H43N5O7 m/z 598.7 (M+H)+; HPLC purity>95% (ret. time, 2.84 min).

Workup

  1. customwas consumed
  2. customthe starting material was consumed
  3. temperaturethe reaction mixture was cooled to room temperature
  4. filtrationThe mixture was filtered through a pad of celite
  5. washthe pad was washed with 40 mL EtOH
  6. concentrationThe solution was concentrated

Sources & evidence

ORD record
ord-a56bb33a269449299f18cc00b4b853e5
Source dataset
uspto-grants-2015_09
Patent number
US09145438B2

Reaction notes

Loading…