Acetic Acid → 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)(ethyl)amino)cyclobutyl)propanoate

HRID 2040726Notes

Reaction equation

HRID 2040726 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][NH:22][CH:23]2[CH2:26][CH:25]([CH2:27][CH2:28][C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:30])[CH2:24]2)[O:12]1.[BH3-]C#N.[Na+].[CH3:43][C:44](O)=O.CC=O>CO.O>[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]([CH3:19])([CH3:20])[O:18][C@@H:14]2[C@@H:13]([CH2:21][N:22]([CH2:43][CH3:44])[CH:23]2[CH2:26][CH:25]([CH2:27][CH2:28][C:29]([O:31][CH2:32][C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)=[O:30])[CH2:24]2)[O:12]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 67775599benzyl 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)amino)cyclobutyl)propanoate

Product 1

HCID 67775204Benzyl 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)(ethyl)amino)cyclobutyl)propanoateYield 66%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
30 °C

Procedure

To a mixture of 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)amino)cyclobutyl)propanoate (3.76 g, 7.2 mmol) and NaBH3CN (5.9 g, 93.6 mmol) in MeOH (40 mL) was added AcOH to adjust to pH=6. Then, 40% MeCHO (8.7 mL, 122.5 mmol) was added and the mixture was stirred at 30° C. for 1.5 h. Water (15 mL) was added and the mixture was concentrated in vacuo. Then, the mixture was extracted with DCM (30 mL×3). The combined organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The crude was purified by SGC (DCM: MeOH=100:1-20:1) to obtain the target (2.6 g, yield: 66%) as a white solid. 1H NMR (500 MHz, MeOD): δH 8.26 (s, 1H), 8.23 (m, 1H), 7.37-7.28 (m, 5H), 6.24 (s, 1H), 5.52-5.49 (m, 1H), 5.10-5.06 (m, 3H), 4.41-4.40 (m, 1H), 3.20-2.90 (m, 2H), 2.80-2.60 (m, 2H), 2.12-1.77 (m, 4H), 1.74-1.60 (m, 3H), 1.39 (s, 3H), 1.26-1.22 (m, 3H), 0.94-0.89 (m, 3H) ppm; ESI-MS (m/z): 551.3 [M+1]+.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. extractionThen, the mixture was extracted with DCM (30 mL×3)
  3. washThe combined organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was purified by SGC (DCM: MeOH=100:1-20:1)
  8. customto obtain the target (2.6 g, yield: 66%) as a white solid

Sources & evidence

ORD record
ord-103bb23577814af6b449d9e893e69640
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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