Benzyl 3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanoate → 3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanoic acid

HRID 511678Notes

Reaction equation

HRID 511678 reaction equation
[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]2[C@@H:13]([CH2:21][N:22]([CH3:39])[CH:23]2[CH2:26][CH:25]([CH2:27][CH2:28][C:29]([O:31]CC3C=CC=CC=3)=[O:30])[CH2:24]2)[O:12]1>C(O)C.[Pd]>[NH2:1][C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@H:11]1[C@@H:15]2[O:16][C:17]([CH3:20])([CH3:19])[O:18][C@@H:14]2[C@@H:13]([CH2:21][N:22]([CH3:39])[CH:23]2[CH2:26][CH:25]([CH2:27][CH2:28][C:29]([OH:31])=[O:30])[CH2:24]2)[O:12]1

Participants

4

Reactant 1

HCID 67774903Benzyl 3-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanoate

Product 1

HCID 677751233-(3-((((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)(methyl)amino)cyclobutyl)propanoic acidYield 86%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Benzyl 3-[3-({[(3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxol-4-yl]methyl}(methyl)amino)cyclobutyl]propanoate (1.19 g, 2.22 mmol) was dissolved in ethanol (24 ml) and 10% palladium on charcoal (50% wet paste) (0.24 g) added. The suspension was stirred under an atmosphere of hydrogen for 18 h. It was then filtered and the solid washed with ethanol (10 ml). As the reaction was incomplete, further palladium on charcoal (0.21 g) was added and the reaction continued under hydrogen for a further 24 h. Filtered through double glass fibre, washed with ethanol and evaporated to dryness to give the desired compound as a white foam (mix of diastereomers) (0.85 g, 86%): MS (ESI+) for C21H30N6O5 m/z 447.5 [M+H]+; LC purity 86% (ret. time, 1.08 min); 1H NMR (500 MHz, d4-MeOD) δH 8.18-8.35 (m, 2H), 6.14-6.30 (m, 1H), 5.25-5.56 (m, 1H), 5.01-5.11 (m, 1H), 4.35-4.52 (m, 1H), 3.63-3.81 (m, 1H), 3.24-3.30 (m, 1H), 2.98-3.16 (m, 1H), 2.89 (ddd, J=17.2, 13.4, 3.7 Hz, 1H), 2.36 (m, 2H), 2.17-2.26 (m, 1H), 1.98-2.17 (m, 3H), 1.67-1.92 (m, 3H), 1.49-1.64 (m, 4H), 1.39 (s, 3H), 1.20-1.33 (m, 1H).

Workup

  1. filtrationIt was then filtered
  2. washthe solid washed with ethanol (10 ml)
  3. additionfurther palladium on charcoal (0.21 g) was added
  4. waitthe reaction continued under hydrogen for a further 24 h
  5. filtrationFiltered through double glass fibre
  6. washwashed with ethanol
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-4829957d859147e7ad09f99a97e34aba
Source dataset
uspto-grants-2015_08
Patent number
US09096634B2

Reaction notes

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