Pyridine → HCID 44462713, compound

HRID 2361651Notes

Reaction equation

HRID 2361651 reaction equation
C1C([N+]([O-])=O)=CC=C([Cl-][C:11]([O-])=[O:12])C=1.[CH:14]1([N:18]2[CH2:24][CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[CH2:17][CH2:16][CH2:15]1.N1C=CC=CC=1.Cl.[NH:32]1[CH2:35][CH:34]([OH:36])[CH2:33]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:14]1([N:18]2[CH2:24][CH2:23][CH2:22][N:21]([C:11]([N:32]3[CH2:35][CH:34]([OH:36])[CH2:33]3)=[O:12])[CH2:20][CH2:19]2)[CH2:17][CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 574239531-Cyclobutyl-[1,4]diazepane

Product 1

HCID 44462713HCID 44462713, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred RT solution of 4-nitrophenylchloroformate (2.63 g, 13.05 mmol) in DCM (10 ml) was added drop wise a solution of 1-cyclobutyl-1,4-diazepane (1.83 g, 11.86 mmol) and pyridine (1.03 g, 13.05 mmol) in DCM (2 ml). The resulting mixture was stirred at RT for approximately 3 days. The solvent was evaporated in vacuo and the residue dissolved in MeOH/IPA (1:3, 40 ml). Azetidin-3-ol hydrochloride (1.3 g, 11.86 mmol) and DIPEA (3.37 g, 26.1 mmol) were added and the resulting mixture was heated to reflux (˜90° C.) overnight. After cooling to RT, the solvent was evaporated and the residue partitioned between DCM (40 ml) and 2M K2CO3 aq (20 ml). The organic layer was separated and the aq. phase re-extracted with DCM (20 ml). The combined organic phases were dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by silica flash column chromatography (eluting with DCM/MeOH/NH3 90:10:1) provided the title compound as yellow solid (1.16 g, 39%).

Workup

  1. customThe solvent was evaporated in vacuo
  2. dissolutionthe residue dissolved in MeOH/IPA (1:3, 40 ml)
  3. temperaturethe resulting mixture was heated
  4. temperatureto reflux (˜90° C.) overnight
  5. temperatureAfter cooling to RT
  6. customthe solvent was evaporated
  7. customthe residue partitioned between DCM (40 ml) and 2M K2CO3 aq (20 ml)
  8. customThe organic layer was separated
  9. extractionthe aq. phase re-extracted with DCM (20 ml)
  10. dry with materialThe combined organic phases were dried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customPurification
  14. washby silica flash column chromatography (eluting with DCM/MeOH/NH3 90:10:1)

Sources & evidence

ORD record
ord-19d9672fa6a247bb9dd07973ba03e9f4
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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