Acetonitrile → HCID 67818376, compound

HRID 1024658Notes

Reaction equation

HRID 1024658 reaction equation
[CH3:1][O:2][C:3]1[CH:44]=[C:43]([O:45][CH3:46])[CH:42]=[CH:41][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]([CH3:40])S(C4C=CC=CC=4[N+]([O-])=O)(=O)=O)[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(#N)C.C1(S)C=CC=CC=1>>[CH3:1][O:2][C:3]1[CH:44]=[C:43]([O:45][CH3:46])[CH:42]=[CH:41][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[C@H:19]([O:23][C:22]([CH3:25])([CH3:24])[O:21]4)[C@@H:18]([CH2:26][NH:27][CH3:40])[O:17]3)[C:9]=2[N:10]=[CH:11][N:12]=1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 7969ThiophenolHCID 10796Cesium carbonateHCID 67814681HCID 67814681, compound

Product 1

HCID 67818376HCID 67818376, compoundYield 56.8%

Procedure

A suspension of N-(((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)-N-methyl-2-nitrobenzenesulfonamide (0.82 g, 1.2 mmol) and cesium carbonate (0.82 g, 2.5 mmol) in acetonitrile (23 mL, 440 mmol) was degassed by sparging with nitrogen gas for 10 minutes. The solution was treated dropwise with benzenethiol (0.26 mL, 2.5 mmol) and the mixture was allowed to stir at room temperature overnight. After 22 h, LCMS indicated the reaction was complete. The reaction mixture was partitioned between 60 mL 1N NaOH and 120 mL CH2Cl2, the layers separated and the aqueous phase was washed with three 25 mL portions of CH2Cl2. The combined organic phase was dried over MgSO4, filtered, and concentrated to an oil. The material was purified by flash chromatography (80 g silica gel, 0-5% 7N NH3 in CH3OH/CH2Cl2) to yield the title compound (320 mg, 54%) as a foam: MS (ESI+) for C24H31N5O6 m/z 470.1 (M+H)+; (ESI−) for C24H31N5O6 m/z 468.0 (M−H)−; HPLC purity 99% (ret. time, 2.67 min).

Workup

  1. customwas degassed
  2. customby sparging with nitrogen gas for 10 minutes
  3. waitAfter 22 h
  4. customThe reaction mixture was partitioned between 60 mL 1N NaOH and 120 mL CH2Cl2
  5. customthe layers separated
  6. washthe aqueous phase was washed with three 25 mL portions of CH2Cl2
  7. dry with materialThe combined organic phase was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated to an oil
  10. customThe material was purified by flash chromatography (80 g silica gel, 0-5% 7N NH3 in CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-1852b256f3f24470aebdf8692b19ee63
Source dataset
uspto-grants-2014_05
Patent number
US08722877B2

Reaction notes

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