Hydrochloric Acid → HCID 86762624, compound

HRID 2409060Notes

Reaction equation

HRID 2409060 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:10]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[CH:9]=[CH:8][C:6]=2[N:7]=1.C([Sn](CCCC)(CCCC)[C:24]([O:26]CC)=[CH2:25])CCC.Cl.[OH-].[Na+]>CN(C=O)C.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:16][Si:15]([CH3:18])([CH3:17])[CH2:14][CH2:13][O:12][CH2:11][N:10]1[C:5]2[CH:4]=[N:3][C:2]([C:24](=[O:26])[CH3:25])=[N:7][C:6]=2[CH:8]=[CH:9]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 619414Stannane, tributyl(1-ethoxyethenyl)-HCID 86762623HCID 86762623, compound

Product 1

HCID 86762624HCID 86762624, compoundYield 66%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred mixture of sodium hydride (12.5 g, 520 mmol, 60% in mineral oil) in anhydrous THF (300 mL) at 0° C. was added dropwise 2-chloro-5H-pyrrolo[3,2-d]pyrimidine (40.0 g, 262 mmol) dissolved in anhydrous THF (200 mL). The reaction mixture was stirred at 0° C. for 15 min them SEMCl (52.5 g, 315 mmol) was added dropwise. The mixture was then stirred at RT for 1 h and then diluted with EtOAc. The organic layer was washed with water and brine, dried over (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified by SiO2 chromatography to afford 42 g (56.4%) of 2-chloro-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-d]pyrimidine as an orange oil. A high-pressure tube charged with 2-chloro-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-d]pyrimidine (2.23 g, 7.90 mmol), tributyl(1-ethoxyvinyl)stannane (3.7 g, 10.27 mmol), and Pd(PPh3)2Cl2 (200 mg) in degassed DMF (20 mL) under N2 was sealed and heated at 100° C. for 16 h. The reaction mixture was cooled, diluted with EtOAc, and filtered through a pad of Celite® to remove Pd solid. The filtrate was washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was dissolved in anhydrous THF (0.3 M), and 2N HCl (5.0 eq.) was added. The reaction mixture was stirred at RT under N2 for 16 h, poured into 10% aq. NaOH solution, and then extracted with EtOAc. The organic layer was washed with water and brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by SiO2 chromatography to afford 1.5 g (66%) of 1-(5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[3,2-d]pyrimidin-2-yl)ethanone as pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H), 7.66 (d, J=3.2 Hz, 1H), 6.89 (d, J=4.8 Hz, 1H), 5.60 (s, 2H), 3.49 (t, J=8.0 Hz, 2H), 2.88 (s, 3H), 0.901 (t, J=8.0 Hz, 2H), −0.053 (s, 9H); MS (ESI) m/z: 291 [M+].

Workup

  1. customwas sealed
  2. temperatureThe reaction mixture was cooled
  3. filtrationfiltered through a pad of Celite®
  4. customto remove Pd solid
  5. washThe filtrate was washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. dissolutionThe crude product was dissolved in anhydrous THF (0.3 M)
  10. extractionextracted with EtOAc
  11. washThe organic layer was washed with water and brine
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe crude product was purified by SiO2 chromatography

Sources & evidence

ORD record
ord-d16a047c0a344823821f772ed0bd6da4
Source dataset
uspto-grants-2014_08
Patent number
US08815877B2

Reaction notes

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