Tetrahydrofuran → HCID 131734499, compound

HRID 590872Notes

Reaction equation

HRID 590872 reaction equation
C[C:2]([CH3:5])([O-])[CH3:3].[Na+].Cl[C:8]1[N:13]=[CH:12][C:11]2[C:14]([NH:36][C:37](=[O:40])[O:38][CH3:39])=[N:15][N:16]([C:17]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:10]=2[CH:9]=1.[C:41](=[O:51])([O:43][CH2:44]C1C=CC=CC=1)[NH2:42].[CH2:52]1[CH2:56]OC[CH2:53]1>>[C:17]([N:16]1[C:10]2[CH:9]=[C:8]([NH:42][C:41](=[O:51])[O:43][CH3:44])[N:13]=[CH:12][C:11]=2[C:14]([NH:36][C:37](=[O:40])[O:38][CH2:39][C:3]2[CH:2]=[CH:5][CH:56]=[CH:52][CH:53]=2)=[N:15]1)([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 12136Benzyl carbamateHCID 23676156Sodium t-butoxideHCID 118390794HCID 118390794, compound

Product 1

HCID 131734499HCID 131734499, compoundYield 40.2%

Conditions

Temperature
50 °C

Procedure

A 20 mL microwave vial was charged with sodium tert-butoxide (103 mg, 1.075 mmol), methyl (6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridin-3-yl)carbamate (252 mg, 0.537 mmol), benzyl carbamate (122 mg, 0.806 mmol) and BrettPhos-G3-Pd (24.36 mg, 0.027 mmol). THF (6 ml) was added, the vial was flushed with argon, capped and the contents heated to 50° C. with stirring for 10 h. LCMS analysis indicated incomplete conversion to the desired product. Excess benzyl carbamate (61 mg), sodium tert-butoxide (51 mg) and BrettPhos-G3-Pd (12 mg) was added. The vial was flushed with argon, capped and the contents heated to 50° C. for an additional 4 h. The mixture was cooled, diluted with ethyl acetate (10 mL), washed with saturated aqueous sodium hydrogen carbonate (2×20 mL), dried (MgSO4), filtered and the solvent evaporated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel (ISCO; 24 g prepacked) eluting with ethyl acetate/hexanes to afford benzyl methyl (1-trityl-1H-pyrazolo[4,3-c]pyridine-3,6-diyl)dicarbamate (126 mg, 0.216 mmol, 40.2% yield) as a white solid. MS ESI calc'd. For C35H30N5O4 [M+H]+ 584. found 584.

Workup

  1. customthe vial was flushed with argon
  2. customcapped
  3. additionExcess benzyl carbamate (61 mg), sodium tert-butoxide (51 mg) and BrettPhos-G3-Pd (12 mg) was added
  4. customThe vial was flushed with argon
  5. customcapped
  6. temperaturethe contents heated to 50° C. for an additional 4 h
  7. temperatureThe mixture was cooled
  8. additiondiluted with ethyl acetate (10 mL)
  9. washwashed with saturated aqueous sodium hydrogen carbonate (2×20 mL)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. customthe solvent evaporated under reduced pressure
  13. customThe resulting residue was purified by flash column chromatography on silica gel (ISCO; 24 g prepacked)
  14. washeluting with ethyl acetate/hexanes

Sources & evidence

ORD record
ord-744eab2acaeb4ec582d63aa72767da70
Source dataset
uspto-grants-2016_01
Patent number
US09233979B2

Reaction notes

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