Sodium Carbonate → HCID 178453592, compound

HRID 1969688Notes

Reaction equation

HRID 1969688 reaction equation
S(Cl)(Cl)=O.[C:5]([O:9][C:10](=[O:43])[NH:11][CH2:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([CH2:19][C:20](=O)[NH:21][NH:22][C:23]2[N:24]=[C:25]3[CH:31]=[CH:30][N:29](S(C4C=CC(C)=CC=4)(=O)=O)[C:26]3=[N:27][CH:28]=2)[CH2:15][CH2:14]1)([CH3:8])([CH3:7])[CH3:6].C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>O.O1CCOCC1>[C:5]([O:9][C:10](=[O:43])[NH:11][CH2:12][C@H:13]1[CH2:18][CH2:17][C@H:16]([CH2:19][C:20]2[N:24]3[C:25]4[CH:31]=[CH:30][NH:29][C:26]=4[N:27]=[CH:28][C:23]3=[N:22][N:21]=2)[CH2:15][CH2:14]1)([CH3:8])([CH3:7])[CH3:6]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 24386Thionyl ChlorideHCID 178427352HCID 178427352, compound

Product 1

HCID 178453592HCID 178453592, compoundYield 64.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Thionyl chloride (0.030 mL, 0.41 mmol) was added dropwise to a solution of tert-butyl(trans-4-(2-oxo-2-(2-(5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)hydrazinyl)ethyl)cyclohexyl)methyl-carbamate (0.127 g, 0.228 mmol, prepared using M from trans-(4-aminomethylcyclohexyl)acetic acid hydrochloride [AstaTech], H from Example #1, Step D, HATU, TEA), TEA (0.160 mL, 1.15 mmol), and 1,4-dioxane (2.3 mL) under nitrogen. A reflux condenser was attached and the reaction mixture was warmed to about 80° C. After about 2 h, the solution was cooled to ambient temperature and aqueous Na2CO3 (2 M, 3.4 mL, 6.8 mmol) was added and the biphasic mixture was warmed to about 80° C. After about 2 h, aqueous NaOH (2 M, 0.570 mL, 1.14 mmol) was added due to slow rate of deprotection. After about 17 h, the mixture was allowed to cool to ambient temperature. The reaction solution was diluted with water (5 mL) and then extracted with EtOAc (2×10 mL). The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 2-8% MeOH in DCM to give tert-butyl(trans-4-((6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)methyl)cyclohexyl)methylcarbamate (0.0565 g, 63%): LC/MS (Table 1, Method a) Rt=1.85 min; MS m/z: 385 (M+H)+.

Workup

  1. customA reflux condenser was attached
  2. temperaturethe solution was cooled to ambient temperature
  3. temperaturethe biphasic mixture was warmed to about 80° C
  4. waitAfter about 2 h
  5. waitAfter about 17 h
  6. temperatureto cool to ambient temperature
  7. extractionextracted with EtOAc (2×10 mL)
  8. dry with materialThe combined organics were dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel chromatography
  12. washeluting with a gradient of 2-8% MeOH in DCM

Sources & evidence

ORD record
ord-4b7cdbc6d75b4e778f05092d16e7f673
Source dataset
uspto-grants-2013_04
Patent number
US08426411B2

Reaction notes

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