Hydrochloric Acid → HCID 178422167, compound

HRID 2095741Notes

Reaction equation

HRID 2095741 reaction equation
[Si]([O:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([N:15]2[C:19]([CH3:20])=[C:18]([C:21]3[CH:22]=[C:23]4[C:29]([CH:30]([C:51]5[C:56]([Cl:57])=[CH:55][CH:54]=[C:53]([F:58])[C:52]=5[Cl:59])[C:31]([F:50])(S(C5C=CC=CC=5)(=O)=O)S(C5C=CC=CC=5)(=O)=O)=[CH:28][NH:27][C:24]4=[N:25][CH:26]=3)[CH:17]=[N:16]2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.P([O-])([O-])(O)=O.[Na+].[Na+].CO.Cl.C([O-])(O)=O.[Na+]>C1COCC1.[Na].[Hg].C(Cl)Cl>[Cl:59][C:52]1[C:53]([F:58])=[CH:54][CH:55]=[C:56]([Cl:57])[C:51]=1[CH:30]([C:29]1[C:23]2[C:24](=[N:25][CH:26]=[C:21]([C:18]3[CH:17]=[N:16][N:15]([C@H:12]4[CH2:13][CH2:14][C@H:9]([OH:8])[CH2:10][CH2:11]4)[C:19]=3[CH3:20])[CH:22]=2)[NH:27][CH:28]=1)[CH2:31][F:50]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 887MethanolHCID 24203Sodium Phosphate, DibasicHCID 516892Sodium BicarbonateHCID 178422165HCID 178422165, compound

Product 1

HCID 178422167HCID 178422167, compound

Reagents, catalysts & solvents 3

HCID 9837419Sodium amalgamCatalystHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 5-[1-(trans-4-{[tert-butyl(dimethyl)silyl]oxy}cyclohexyl)-5-methyl-1H-pyrazol-4-yl]-3-[1-(2,6-dichloro-3-fluorophenyl)-2-fluoro-2,2-bis(phenylsulfonyl)ethyl]-1H-pyrrolo[2,3-b]pyridine (30.00 mg, 0.03333 mmol) and Disodium hydrogen phosphate (94.64 mg, 0.6667 mmol) in methanol (5.00 mL, 123 mmol) and THF (0.300 mL, 3.70 mmol) at −20° C. was added Sodium Mercury Amalgam (5% sodium; 0.28 g, 0.67 mmol). The resulting mixture was stirred between −15° C. and −5° C. for 1.5 h. The mixture was transferred into another flask by filtration to remove the inorganic insolubles. Sat. aq. solution of NH4Cl (2 ml) was added to the MeOH mixture, then the solvent was removed under reduced pressure to give a residue, which was diluted by DCM and extracted by DCM (20 mL×3). The organic phase were combined, dried and concentrated to give a desulfonylated intermediate [MS (ES+): m/z 619.23, 621.23 [MH+]. HPLC: tR=2.02 min (polar—3 min, TOF)]. This intermediate was dissolved in THF (0.3 mL) at 0° C., 2.0 M aq. HCl (0.50 mL, 1.0 mmol) was added, and the resulting mixture was stirred at rt for 30 min. NaHCO3 (112.0 mg, 1.333 mmol) was added to the mixture slowly to adjust pH=≈9. Then the solvent was removed under reduced pressure to give a residue, which was diluted by DCM and extracted by DCM (20 mL×3). The organic phase were combined, dried and concentrated to give a crude residue which was purified by silica gel chromatography (eluent: 5% MeOH in DCM) to give the title compound. 1H NMR (400 MHz, CD3OD): δ=1.48-1.60 (m, 2H), 1.94-2.16 (m, 6H), 2.26 (s, 3H), 3.63-3.77 (m, 1H), 4.15-4.28 (m, 1H), 5.20-5.54 (m, 2H), 5.62-5.75 (m, 1H), 7.28 (t, J=8.6 Hz, 1H), 7.35-7.64 (m, 4H), 8.20 (d, J=2.0 Hz, 1H). MS (ES+): m/z 505.06, 507.07 [MH+]. HPLC: tR=1.33 min (polar—3 min, TOF).

Workup

  1. filtrationThe mixture was transferred into another flask by filtration
  2. customto remove the inorganic insolubles
  3. additionSat. aq. solution of NH4Cl (2 ml) was added to the MeOH mixture
  4. customthe solvent was removed under reduced pressure
  5. customto give a residue, which
  6. extractionextracted by DCM (20 mL×3)
  7. customdried
  8. concentrationconcentrated
  9. customto give a desulfonylated intermediate [MS (ES+): m/z 619.23, 621.23 [MH+]. HPLC: tR=2.02 min (polar—3 min, TOF)]
  10. stirringthe resulting mixture was stirred at rt for 30 min
  11. customThen the solvent was removed under reduced pressure
  12. customto give a residue, which
  13. extractionextracted by DCM (20 mL×3)
  14. customdried
  15. concentrationconcentrated
  16. customto give a crude residue which
  17. customwas purified by silica gel chromatography (eluent: 5% MeOH in DCM)

Sources & evidence

ORD record
ord-8b32eabb1012439d873c7724e0087909
Source dataset
uspto-grants-2013_05
Patent number
US08445510B2

Reaction notes

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