Hydrochloric Acid → HCID 118159483, compound

HRID 628381Notes

Reaction equation

HRID 628381 reaction equation
[Si]([O:18][CH2:19][C:20]1[CH:21]=[C:22]([CH:66]=[CH:67][CH:68]=1)[CH2:23][N:24]1[C:28]2[CH:29]=[CH:30][C:31]3[N:32]([C:33]([CH3:36])=[N:34][N:35]=3)[C:27]=2[CH:26]=[C:25]1[C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47]O[Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:42]=1)=[O:38])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[ClH:69]>O1CCOCC1>[OH:18][CH2:19][C:20]1[CH:21]=[C:22]([CH:66]=[CH:67][CH:68]=1)[CH2:23][N:24]1[C:28]2[CH:29]=[CH:30][C:31]3[N:32]([C:33]([CH3:36])=[N:34][N:35]=3)[C:27]=2[CH:26]=[C:25]1[C:37]([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][Cl:69])[CH:42]=1)=[O:38]

Participants

4

Reactant 2

HCID 313Hydrochloric Acid2×HCID 123254475HCID 123254475, compound

Product 1

HCID 118159483HCID 118159483, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent3×

Conditions

Temperature
110 °C

Procedure

3-({[tert-Butyl(diphenyl)silyl]oxy}methyl)benzyl 6-[3-({[tert-butyl(diphenyl)silyl]oxy}methyl)benzyl]-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylate (0.890 g, 0.954 mmol, from Step 5) was dissolved in 1,4-dioxane (20 mL) and 4.0 M solution of HCl in dioxane (20 mL, 80 mmol) was added. The reaction was stirred for 1 h at 110° C. Three additional portions of 4.0 M HCl in dioxane (10 mL, 40 mmol) were added periodically over the course of 6.5 hours at 110° C. After the third addition, the reaction mixture was heated at 110° C. in a sealed vessel for 48 hours. When the reaction was complete, the dioxane was evaporated and the residue was neutralized by the addition of saturated NaHCO3 solution. The product was extracted with three portions of EtOAc. The combined organic extracts were dried over sodium sulfate, filtered and concentrated. Flash chromatography, eluting with a gradient from 0-10% MeOH/DCM was used to isolate 3-(chloromethyl)benzyl 6-[3-(hydroxymethyl)benzyl]-1-methyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyridine-7-carboxylate, which was used in the displacement reaction that follows.

Workup

  1. additionAfter the third addition
  2. temperaturethe reaction mixture was heated at 110° C. in a sealed vessel for 48 hours
  3. customthe dioxane was evaporated
  4. additionthe residue was neutralized by the addition of saturated NaHCO3 solution
  5. extractionThe product was extracted with three portions of EtOAc
  6. dry with materialThe combined organic extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash chromatography, eluting with a gradient from 0-10% MeOH/DCM

Sources & evidence

ORD record
ord-86c6098729af4fadbbf4d212c66374be
Source dataset
uspto-grants-2016_04
Patent number
US09309246B2

Reaction notes

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