Hydrochloric Acid → HCID 178521310, compound

HRID 2202749Notes

Reaction equation

HRID 2202749 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:42])[C:7]=1[C:8](=[O:41])[CH2:9][N:10]([CH2:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[C:35]([F:40])[CH:34]=1)[C:11]([C:13]1[CH:14]=[N:15][N:16]([C@H:21]2[CH2:26][CH2:25][C@H:24]([C:27]([O:29]CC)=[O:28])[CH2:23][CH2:22]2)[C:17]=1[CH:18]([F:20])[F:19])=[O:12].Cl.O>O1CCOCC1>[Cl:42][C:6]1[CH:5]=[N:4][CH:3]=[C:2]([Cl:1])[C:7]=1[C:8](=[O:41])[CH2:9][N:10]([CH2:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[C:35]([F:40])[CH:34]=1)[C:11]([C:13]1[CH:14]=[N:15][N:16]([C@H:21]2[CH2:26][CH2:25][C@H:24]([C:27]([OH:29])=[O:28])[CH2:23][CH2:22]2)[C:17]=1[CH:18]([F:19])[F:20])=[O:12]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 178472415HCID 178472415, compound

Product 1

HCID 178521310HCID 178521310, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of compound 20-3 (106 mg, 0.17 mmol) in dioxane (6 mL) was added 6 M HCl (6 mL) and heated at 80° C. for 16 h. The reaction mixture was cooled to room temperature, added H2O and extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine (2×10 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by reverse phase column chromatography (C18 silica gel, 75% CH3CN/water as eluent) to provide the compound of example 20 (36 mg, 62%) as a white solid. 1H NMR (DMSO-d6) rotamers present δ 8.76 and 8.69 (2H, 2×s); 7.77 and 7.67 (1H, 2×s); 7.45-7.00 (4H, m); 4.91-4.70 (4H, m); 4.36-4.29 (1H, m); 2.31-2.24 (1H, m); 2.06-2.02 (2H, m); 1.94-1.89 (4H, m); 1.56-1.45 (2H, m); LCMS (ESI): 599 (M+H)+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (2×50 mL)
  3. washThe combined organic layers were washed with brine (2×10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by reverse phase column chromatography (C18 silica gel, 75% CH3CN/water as eluent)

Sources & evidence

ORD record
ord-3912bea2feb649be807505df751f3fcc
Source dataset
uspto-grants-2016_06
Patent number
US09365522B2

Reaction notes

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