Hydrochloric Acid → HCID 67002720, compound

HRID 2362694Notes

Reaction equation

HRID 2362694 reaction equation
[Cl:1][C:2]1[C:3]([C:34]2[S:38][C:37]([C:39]3([O:43]COC)[CH2:42][CH2:41][CH2:40]3)=[N:36][CH:35]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH:12]=3)[N:8]([S:24]([C:27]3[CH:33]=[CH:32][C:30]([CH3:31])=[CH:29][CH:28]=3)(=[O:26])=[O:25])[C:5]2=[N:6][CH:7]=1.Cl>CO.O1CCCC1>[Cl:1][C:2]1[C:3]([C:34]2[S:38][C:37]([C:39]3([OH:43])[CH2:42][CH2:41][CH2:40]3)=[N:36][CH:35]=2)=[C:4]2[CH:10]=[C:9]([C:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH:12]=3)[N:8]([S:24]([C:27]3[CH:28]=[CH:29][C:30]([CH3:31])=[CH:32][CH:33]=3)(=[O:25])=[O:26])[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 67003701HCID 67003701, compound

Product 1

HCID 67002720HCID 67002720, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of tert-butyl 4-(5-chloro-4-(2-(1-(methoxymethoxy)cyclobutyl)thiazol-5-yl)-1-tosyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (Example 89A) (0.1 g, 0.146 mmol) in methanol (0.7 mL) and tetrahydrofuran (0.25 mL) was treated with 10% aqueous HCl solution (0.165 mL), and the reaction was heated at 65° C. for 5 hours. The reaction was cooled to ambient temperature and concentrated to dryness. The residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The layers were separated, and the aqueous layer was extracted with additional dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The concentrate was purified by flash chromatography on a silica gel column, eluting with a gradient of 0% to 5% methanol in dichloromethane, to provide the title compound. MS ESI(+) m/z 541.0 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. concentrationconcentrated to dryness
  3. customThe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with additional dichloromethane
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe concentrate was purified by flash chromatography on a silica gel column
  10. washeluting with a gradient of 0% to 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-838de0afa35f4bf980c994d9e88e6a59
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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